articles.bib

@article{aagaardPlacentaHarborsUnique2014,
  title = {The Placenta Harbors a Unique Microbiome},
  author = {Aagaard, Kjersti and Ma, Jun and Antony, Kathleen M. and Ganu, Radhika and Petrosino, Joseph and Versalovic, James},
  year = {2014},
  month = may,
  volume = {6},
  pages = {237ra65},
  issn = {1946-6242},
  doi = {10.1126/scitranslmed.3008599},
  abstract = {Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity {$<$}0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth {$<$}37 weeks (P = 0.001).},
  journal = {Science Translational Medicine},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {237},
  pmcid = {PMC4929217},
  pmid = {24848255}
}

@article{adamGrowingTreeArchaea2017,
  title = {The Growing Tree of {{Archaea}}: New Perspectives on Their Diversity, Evolution and Ecology},
  shorttitle = {The Growing Tree of {{Archaea}}},
  author = {Adam, Panagiotis S. and Borrel, Guillaume and {Brochier-Armanet}, C{\'e}line and Gribaldo, Simonetta},
  year = {2017},
  month = nov,
  volume = {11},
  pages = {2407--2425},
  issn = {1751-7370},
  doi = {10.1038/ismej.2017.122},
  abstract = {The Archaea occupy a key position in the Tree of Life, and are a major fraction of microbial diversity. Abundant in soils, ocean sediments and the water column, they have crucial roles in processes mediating global carbon and nutrient fluxes. Moreover, they represent an important component of the human microbiome, where their role in health and disease is still unclear. The development of culture-independent sequencing techniques has provided unprecedented access to genomic data from a large number of so far inaccessible archaeal lineages. This is revolutionizing our view of the diversity and metabolic potential of the Archaea in a wide variety of environments, an important step toward understanding their ecological role. The archaeal tree is being rapidly filled up with new branches constituting phyla, classes and orders, generating novel challenges for high-rank systematics, and providing key information for dissecting the origin of this domain, the evolutionary trajectories that have shaped its current diversity, and its relationships with Bacteria and Eukarya. The present picture is that of a huge diversity of the Archaea, which we are only starting to explore.},
  journal = {The ISME journal},
  keywords = {古菌,里程碑},
  language = {eng},
  number = {11},
  pmcid = {PMC5649171},
  pmid = {28777382}
}

@article{ahnHumanGutMicrobiome2013,
  title = {Human {{Gut Microbiome}} and {{Risk}} for {{Colorectal Cancer}}},
  author = {Ahn, Jiyoung and Sinha, Rashmi and Pei, Zhiheng and Dominianni, Christine and Wu, Jing and Shi, Jianxin and Goedert, James J. and Hayes, Richard B. and Yang, Liying},
  year = {2013},
  month = dec,
  volume = {105},
  pages = {1907--1911},
  publisher = {{Oxford Academic}},
  issn = {0027-8874},
  doi = {10.1093/jnci/djt300},
  abstract = {Abstract.   We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subj},
  journal = {JNCI: Journal of the National Cancer Institute},
  language = {en},
  number = {24}
}

@article{arpaiaMetabolitesProducedCommensal2013,
  title = {Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory {{T}}-Cell Generation},
  author = {Arpaia, Nicholas and Campbell, Clarissa and Fan, Xiying and Dikiy, Stanislav and {van der Veeken}, Joris and {deRoos}, Paul and Liu, Hui and Cross, Justin R. and Pfeffer, Klaus and Coffer, Paul J. and Rudensky, Alexander Y.},
  year = {2013},
  month = dec,
  volume = {504},
  pages = {451--455},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature12726},
  abstract = {In mice, provision of butyrate\textemdash a short-chain fatty acid produced by commensal microorganisms during starch fermentation\textemdash facilitates extrathymic generation and differentiation of Foxp3+ regulatory T cells, demonstrating that metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells.},
  copyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7480}
}

@article{arumugamEnterotypesHumanGut2011,
  title = {Enterotypes of the Human Gut Microbiome},
  author = {Arumugam, Manimozhiyan and Raes, Jeroen and Pelletier, Eric and Le Paslier, Denis and Yamada, Takuji and Mende, Daniel R. and Fernandes, Gabriel R. and Tap, Julien and Bruls, Thomas and Batto, Jean-Michel and Bertalan, Marcelo and Borruel, Natalia and Casellas, Francesc and Fernandez, Leyden and Gautier, Laurent and Hansen, Torben and Hattori, Masahira and Hayashi, Tetsuya and Kleerebezem, Michiel and Kurokawa, Ken and Leclerc, Marion and Levenez, Florence and Manichanh, Chaysavanh and Nielsen, H. Bj{\o}rn and Nielsen, Trine and Pons, Nicolas and Poulain, Julie and Qin, Junjie and {Sicheritz-Ponten}, Thomas and Tims, Sebastian and Torrents, David and Ugarte, Edgardo and Zoetendal, Erwin G. and Wang, Jun and Guarner, Francisco and Pedersen, Oluf and {de Vos}, Willem M. and Brunak, S{\o}ren and Dor{\'e}, Joel and Weissenbach, Jean and Ehrlich, S. Dusko and Bork, Peer},
  year = {2011},
  month = may,
  volume = {473},
  pages = {174--180},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature09944},
  abstract = {The human gut microbiota consists of a huge number of species and varies greatly between individuals. A comparative metagenomic analysis of the human gut microbiomes of 39 individuals from 6 countries shows that despite this diversity, the microbiota composition can be classified into at least 3 distinct groups, or enterotypes. The enterotypes contain functional markers that correlate with individual features such as age and body mass index, a feature that may be of use in the diagnosis of numerous human disorders such as colorectal cancer and diabetes.},
  copyright = {2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  keywords = {菌群稳定性,里程碑},
  language = {en},
  number = {7346}
}

@article{ashManipulatingMicrobiota2016,
  title = {Manipulating the {{Microbiota}}},
  author = {Ash, C. and Mueller, K.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {530--531},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.352.6285.530},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{atarashiInductionColonicRegulatory2011,
  title = {Induction of {{Colonic Regulatory T Cells}} by {{Indigenous Clostridium Species}}},
  author = {Atarashi, Koji and Tanoue, Takeshi and Shima, Tatsuichiro and Imaoka, Akemi and Kuwahara, Tomomi and Momose, Yoshika and Cheng, Genhong and Yamasaki, Sho and Saito, Takashi and Ohba, Yusuke and Taniguchi, Tadatsugu and Takeda, Kiyoshi and Hori, Shohei and Ivanov, Ivaylo I. and Umesaki, Yoshinori and Itoh, Kikuji and Honda, Kenya},
  year = {2011},
  month = jan,
  volume = {331},
  pages = {337--341},
  publisher = {{American Association for the Advancement of Science}},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.1198469},
  abstract = {CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor\textendash{$\beta$} and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy. Bacteria of the genus Clostridium promote the induction of suppressor T cells in the colons of mice. Bacteria of the genus Clostridium promote the induction of suppressor T cells in the colons of mice.},
  chapter = {Report},
  copyright = {Copyright \textcopyright{} 2011, American Association for the Advancement of Science},
  journal = {Science},
  language = {en},
  number = {6015},
  pmid = {21205640}
}

@article{backhedDynamicsStabilizationHuman2015,
  title = {Dynamics and {{Stabilization}} of the {{Human Gut Microbiome}} during the {{First Year}} of {{Life}}},
  author = {B{\"a}ckhed, Fredrik and Roswall, Josefine and Peng, Yangqing and Feng, Qiang and Jia, Huijue and {Kovatcheva-Datchary}, Petia and Li, Yin and Xia, Yan and Xie, Hailiang and Zhong, Huanzi and Khan, Muhammad Tanweer and Zhang, Jianfeng and Li, Junhua and Xiao, Liang and {Al-Aama}, Jumana and Zhang, Dongya and Lee, Ying Shiuan and Kotowska, Dorota and Colding, Camilla and Tremaroli, Valentina and Yin, Ye and Bergman, Stefan and Xu, Xun and Madsen, Lise and Kristiansen, Karsten and Dahlgren, Jovanna and Wang, Jun},
  year = {2015},
  month = may,
  volume = {17},
  pages = {690--703},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.04.004},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{backhedGutMicrobiotaEnvironmental2004,
  title = {The Gut Microbiota as an Environmental Factor That Regulates Fat Storage},
  author = {B{\"a}ckhed, Fredrik and Ding, Hao and Wang, Ting and Hooper, Lora V. and Koh, Gou Young and Nagy, Andras and Semenkovich, Clay F. and Gordon, Jeffrey I.},
  year = {2004},
  month = nov,
  volume = {101},
  pages = {15718--15723},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.0407076101},
  abstract = {New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60\% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.},
  chapter = {Biological Sciences},
  copyright = {Copyright \textcopyright{} 2004, The National Academy of Sciences.                       Freely available online through the PNAS open access option.},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {44},
  pmid = {15505215}
}

@article{backhedMechanismsUnderlyingResistance2007,
  title = {Mechanisms Underlying the Resistance to Diet-Induced Obesity in Germ-Free Mice},
  author = {B{\"a}ckhed, Fredrik and Manchester, Jill K. and Semenkovich, Clay F. and Gordon, Jeffrey I.},
  year = {2007},
  month = jan,
  volume = {104},
  pages = {979--984},
  issn = {0027-8424},
  doi = {10.1073/pnas.0605374104},
  abstract = {The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  language = {eng},
  number = {3},
  pmcid = {PMC1764762},
  pmid = {17210919}
}

@article{bashirTolllikeReceptorSignaling2004,
  title = {Toll-like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy},
  author = {Bashir, Mohamed Elfatih H. and Louie, Steve and Shi, Hai Ning and {Nagler-Anderson}, Cathryn},
  year = {2004},
  month = jun,
  volume = {172},
  pages = {6978--6987},
  issn = {0022-1767},
  doi = {10.4049/jimmunol.172.11.6978},
  abstract = {The mechanisms by which signaling by the innate immune system controls susceptibility to allergy are poorly understood. In this report, we show that intragastric administration of a food allergen with a mucosal adjuvant induces allergen-specific IgE, elevated plasma histamine levels, and anaphylactic symptoms in three different strains of mice lacking a functional receptor for bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic controls. Susceptibility to allergy correlates with a Th2-biased cytokine response in both the mucosal (mesenteric lymph node and Peyer's patch) and systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are not inherently impaired in their ability to regulate Th1 cytokine production because they respond to stimulation via TLR9. Coadministration of CpG oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1-polarized cytokine response. When the composition of the bacterial flora is reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4 wild-type mice become as susceptible to the induction of allergy as their TLR4-mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are reduced in antibiotic-treated mice in which the flora has been allowed to repopulate. Taken together, our results suggest that TLR4-dependent signals provided by the intestinal commensal flora inhibit the development of allergic responses to food Ags.},
  journal = {Journal of Immunology (Baltimore, Md.: 1950)},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {11},
  pmid = {15153518}
}

@article{bikMolecularAnalysisBacterial2006,
  title = {Molecular Analysis of the Bacterial Microbiota in the Human Stomach},
  author = {Bik, Elisabeth M. and Eckburg, Paul B. and Gill, Steven R. and Nelson, Karen E. and Purdom, Elizabeth A. and Francois, Fritz and {Perez-Perez}, Guillermo and Blaser, Martin J. and Relman, David A.},
  year = {2006},
  month = jan,
  volume = {103},
  pages = {732--737},
  issn = {0027-8424},
  doi = {10.1073/pnas.0506655103},
  abstract = {The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of 128 phylotypes was identified, featuring diversity at this site greater than previously described. The majority of sequences were assigned to the Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria phyla. Ten percent of the phylotypes were previously uncharacterized, including a Deinococcus-related organism, relatives of which have been found in extreme environments but not reported before in humans. The gastric clone libraries from 19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested positive for H. pylori by conventional laboratory methods. Statistical analysis revealed a large degree of intersubject variability of the gastric ecosystem. The presence of H. pylori did not affect the composition of the gastric community. This gastric bacterial rDNA data set was significantly different from sequence collections of the human mouth and esophagus described in other studies, indicating that the human stomach may be home to a distinct microbial eco-system. The gastric microbiota may play important, as-yet-undiscovered roles in human health and disease.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC1334644},
  pmid = {16407106}
}

@article{blaserAntibioticUseIts2016,
  title = {Antibiotic Use and Its Consequences for the Normal Microbiome},
  author = {Blaser, M. J.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {544--545},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad9358},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{bokulichAntibioticsBirthMode2016,
  title = {Antibiotics, Birth Mode, and Diet Shape Microbiome Maturation during Early Life},
  author = {Bokulich, Nicholas A. and Chung, Jennifer and Battaglia, Thomas and Henderson, Nora and Jay, Melanie and Li, Huilin and D Lieber, Arnon and Wu, Fen and {Perez-Perez}, Guillermo I. and Chen, Yu and Schweizer, William and Zheng, Xuhui and Contreras, Monica and {Dominguez-Bello}, Maria Gloria and Blaser, Martin J.},
  year = {2016},
  month = jun,
  volume = {8},
  pages = {343ra82},
  issn = {1946-6242},
  doi = {10.1126/scitranslmed.aad7121},
  abstract = {Early childhood is a critical stage for the foundation and development of both the microbiome and host. Early-life antibiotic exposures, cesarean section, and formula feeding could disrupt microbiome establishment and adversely affect health later in life. We profiled microbial development during the first 2 years of life in a cohort of 43 U.S. infants and identified multiple disturbances associated with antibiotic exposures, cesarean section, and formula feeding. These exposures contributed to altered establishment of maternal bacteria, delayed microbiome development, and altered {$\alpha$}-diversity. These findings illustrate the complexity of early-life microbiome development and its sensitivity to perturbation.},
  journal = {Science Translational Medicine},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {343},
  pmcid = {PMC5308924},
  pmid = {27306664}
}

@article{bondarRegulationMucosalImmunity2019,
  title = {Regulation of Mucosal Immunity by the Microbiota},
  author = {Bondar, Tanya},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00014-2},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  keywords = {粘膜免疫,里程碑},
  language = {en}
}

@article{borrelGenomicsMetagenomicsTrimethylamineutilizing2017,
  title = {Genomics and Metagenomics of Trimethylamine-Utilizing {{Archaea}} in the Human Gut Microbiome},
  author = {Borrel, Guillaume and McCann, Angela and Deane, Jennifer and Neto, Marta C. and Lynch, Denise B. and Brug{\`e}re, Jean-Fran{\c c}ois and O'Toole, Paul W.},
  year = {2017},
  month = sep,
  volume = {11},
  pages = {2059--2074},
  issn = {1751-7370},
  doi = {10.1038/ismej.2017.72},
  abstract = {The biological significance of Archaea in the human gut microbiota is largely unclear. We recently reported genomic and biochemical analyses of the Methanomassiliicoccales, a novel order of methanogenic Archaea dwelling in soil and the animal digestive tract. We now show that these Methanomassiliicoccales are present in published microbiome data sets from eight countries. They are represented by five Operational Taxonomic Units present in at least four cohorts and phylogenetically distributed into two clades. Genes for utilizing trimethylamine (TMA), a bacterial precursor to an atherosclerogenic human metabolite, were present in four of the six novel Methanomassiliicoccales genomes assembled from ELDERMET metagenomes. In addition to increased microbiota TMA production capacity in long-term residential care subjects, abundance of TMA-utilizing Methanomassiliicoccales correlated positively with bacterial gene count for TMA production and negatively with fecal TMA concentrations. The two large Methanomassiliicoccales clades have opposite correlations with host health status in the ELDERMET cohort and putative distinct genomic signatures for gut adaptation.},
  journal = {The ISME journal},
  keywords = {古菌,里程碑},
  language = {eng},
  number = {9},
  pmcid = {PMC5563959},
  pmid = {28585938}
}

@article{brunelloGutMicrobiotaTransfer2019,
  title = {Gut Microbiota Transfer Experiments in Germ-Free Animals},
  author = {Brunello, Lucia},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00009-z},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  keywords = {无菌动物,里程碑},
  language = {en}
}

@article{caniChangesGutMicrobiota2008,
  title = {Changes in {{Gut Microbiota Control Metabolic Endotoxemia}}-{{Induced Inflammation}} in {{High}}-{{Fat Diet}}\textendash{{Induced Obesity}} and {{Diabetes}} in {{Mice}}},
  author = {Cani, Patrice D. and Bibiloni, Rodrigo and Knauf, Claude and Waget, Aur{\'e}lie and Neyrinck, Audrey M. and Delzenne, Nathalie M. and Burcelin, R{\'e}my},
  year = {2008},
  month = jun,
  volume = {57},
  pages = {1470--1481},
  publisher = {{American Diabetes Association}},
  issn = {0012-1797, 1939-327X},
  doi = {10.2337/db07-1403},
  abstract = {OBJECTIVE\textemdash Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. RESEARCH DESIGN AND METHODS\textemdash We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. RESULTS\textemdash We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat\textendash fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14-/- mutant mice mimicked the metabolic and inflammatory effects of antibiotics. CONCLUSIONS\textemdash This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.},
  chapter = {Metabolism},
  copyright = {DIABETES},
  journal = {Diabetes},
  language = {en},
  number = {6},
  pmid = {18305141}
}

@article{caniChangesGutMicrobiota2009,
  title = {Changes in Gut Microbiota Control Inflammation in Obese Mice through a Mechanism Involving {{GLP}}-2-Driven Improvement of Gut Permeability},
  author = {Cani, Patrice D. and Possemiers, S. and de Wiele, T. Van and Guiot, Y. and Everard, A. and Rottier, O. and Geurts, L. and Naslain, D. and Neyrinck, A. and Lambert, D. M. and Muccioli, G. G. and Delzenne, N. M.},
  year = {2009},
  month = aug,
  volume = {58},
  pages = {1091--1103},
  publisher = {{BMJ Publishing Group}},
  issn = {0017-5749, 1468-3288},
  doi = {10.1136/gut.2008.165886},
  abstract = {Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.},
  chapter = {Inflammatory bowel disease},
  copyright = {\textcopyright{} Cani et al 2009. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.},
  journal = {Gut},
  language = {en},
  number = {8},
  pmid = {19240062}
}

@article{caniMetabolicEndotoxemiaInitiates2007,
  title = {Metabolic {{Endotoxemia Initiates Obesity}} and {{Insulin Resistance}}},
  author = {Cani, Patrice D. and Amar, Jacques and Iglesias, Miguel Angel and Poggi, Marjorie and Knauf, Claude and Bastelica, Delphine and Neyrinck, Audrey M. and Fava, Francesca and Tuohy, Kieran M. and Chabo, Chantal and Waget, Aur{\'e}lie and Delm{\'e}e, Evelyne and Cousin, B{\'e}atrice and Sulpice, Thierry and Chamontin, Bernard and Ferri{\`e}res, Jean and Tanti, Jean-Fran{\c c}ois and Gibson, Glenn R. and Casteilla, Louis and Delzenne, Nathalie M. and Alessi, Marie Christine and Burcelin, R{\'e}my},
  year = {2007},
  month = jul,
  volume = {56},
  pages = {1761--1772},
  publisher = {{American Diabetes Association}},
  issn = {0012-1797, 1939-327X},
  doi = {10.2337/db06-1491},
  abstract = {Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat\textendash fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet\textendash induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases.},
  chapter = {Obesity Studies},
  copyright = {DIABETES},
  journal = {Diabetes},
  language = {en},
  number = {7},
  pmid = {17456850}
}

@article{caniSelectiveIncreasesBifidobacteria2007,
  title = {Selective Increases of Bifidobacteria in Gut Microflora Improve High-Fat-Diet-Induced Diabetes in Mice through a Mechanism Associated with Endotoxaemia},
  author = {Cani, Patrice D. and Neyrinck, A. M. and Fava, F. and Knauf, C. and Burcelin, R. G. and Tuohy, K. M. and Gibson, G. R. and Delzenne, N. M.},
  year = {2007},
  month = nov,
  volume = {50},
  pages = {2374--2383},
  issn = {1432-0428},
  doi = {10.1007/s00125-007-0791-0},
  abstract = {Recent evidence suggests that a particular gut microbial community may favour occurrence of the metabolic diseases. Recently, we reported that high-fat (HF) feeding was associated with higher endotoxaemia and lower Bifidobacterium species (spp.) caecal content in mice. We therefore tested whether restoration of the quantity of caecal Bifidobacterium spp. could modulate metabolic endotoxaemia, the inflammatory tone and the development of diabetes.},
  journal = {Diabetologia},
  language = {en},
  number = {11}
}

@article{caporasoMovingPicturesHuman2011,
  title = {Moving Pictures of the Human Microbiome},
  author = {Caporaso, J. Gregory and Lauber, Christian L. and Costello, Elizabeth K. and {Berg-Lyons}, Donna and Gonzalez, Antonio and Stombaugh, Jesse and Knights, Dan and Gajer, Pawel and Ravel, Jacques and Fierer, Noah and Gordon, Jeffrey I. and Knight, Rob},
  year = {2011},
  volume = {12},
  pages = {R50},
  issn = {1474-760X},
  doi = {10.1186/gb-2011-12-5-r50},
  abstract = {BACKGROUND: Understanding the normal temporal variation in the human microbiome is critical to developing treatments for putative microbiome-related afflictions such as obesity, Crohn's disease, inflammatory bowel disease and malnutrition. Sequencing and computational technologies, however, have been a limiting factor in performing dense time series analysis of the human microbiome. Here, we present the largest human microbiota time series analysis to date, covering two individuals at four body sites over 396 timepoints. RESULTS: We find that despite stable differences between body sites and individuals, there is pronounced variability in an individual's microbiota across months, weeks and even days. Additionally, only a small fraction of the total taxa found within a single body site appear to be present across all time points, suggesting that no core temporal microbiome exists at high abundance (although some microbes may be present but drop below the detection threshold). Many more taxa appear to be persistent but non-permanent community members. CONCLUSIONS: DNA sequencing and computational advances described here provide the ability to go beyond infrequent snapshots of our human-associated microbial ecology to high-resolution assessments of temporal variations over protracted periods, within and between body habitats and individuals. This capacity will allow us to define normal variation and pathologic states, and assess responses to therapeutic interventions.},
  journal = {Genome Biology},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {5},
  pmcid = {PMC3271711},
  pmid = {21624126}
}

@article{cashSymbioticBacteriaDirect2006,
  title = {Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin},
  author = {Cash, Heather L. and Whitham, Cecilia V. and Behrendt, Cassie L. and Hooper, Lora V.},
  year = {2006},
  month = aug,
  volume = {313},
  pages = {1126--1130},
  issn = {1095-9203},
  doi = {10.1126/science.1127119},
  abstract = {The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIgamma, a secreted C-type lectin. RegIIIgamma binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIgamma and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships.},
  journal = {Science (New York, N.Y.)},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {5790},
  pmcid = {PMC2716667},
  pmid = {16931762}
}

@article{castellarinFusobacteriumNucleatumInfection2012,
  title = {Fusobacterium Nucleatum Infection Is Prevalent in Human Colorectal Carcinoma},
  author = {Castellarin, Mauro and Warren, Ren{\'e} L. and Freeman, J. Douglas and Dreolini, Lisa and Krzywinski, Martin and Strauss, Jaclyn and Barnes, Rebecca and Watson, Peter and {Allen-Vercoe}, Emma and Moore, Richard A. and Holt, Robert A.},
  year = {2012},
  month = jan,
  volume = {22},
  pages = {299--306},
  publisher = {{Cold Spring Harbor Lab}},
  issn = {1088-9051, 1549-5469},
  doi = {10.1101/gr.126516.111},
  abstract = {An estimated 15\% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 \texttimes{} 10-6), and we observed a positive association with lymph node metastasis.},
  journal = {Genome Research},
  language = {en},
  number = {2},
  pmid = {22009989}
}

@misc{ChangDaoYuJun,
  title = {肠{$\cdot$}道 | 于君：5400字详解大肠癌和菌群关系的5大问题！},
  abstract = {肠道专业人士的招牌演讲，截止2019年8月，已有53位讲者在7期录制中奉献55个精彩演讲。},
  howpublished = {https://www.mr-gut.cn/talks/s/ff4c145befbd4001b1ea59e7c75a367a}
}

@article{chenCiteSpaceIIDetecting2006,
  title = {{{CiteSpace II}}: {{Detecting}} and Visualizing Emerging Trends and Transient Patterns in Scientific Literature},
  shorttitle = {{{CiteSpace II}}},
  author = {Chen, Chaomei},
  year = {2006},
  month = feb,
  volume = {57},
  pages = {359--377},
  issn = {15322882, 15322890},
  doi = {10.1002/asi.20317},
  journal = {Journal of the American Society for Information Science and Technology},
  language = {en},
  number = {3}
}

@article{chuMaturationInfantMicrobiome2017,
  title = {Maturation of the Infant Microbiome Community Structure and Function across Multiple Body Sites and in Relation to Mode of Delivery},
  author = {Chu, Derrick M. and Ma, Jun and Prince, Amanda L. and Antony, Kathleen M. and Seferovic, Maxim D. and Aagaard, Kjersti M.},
  year = {2017},
  month = mar,
  volume = {23},
  pages = {314--326},
  issn = {1546-170X},
  doi = {10.1038/nm.4272},
  abstract = {Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal-infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R2 = 0.038), this was not true for neonatal stool (meconium; Mann-Whitney P {$>$} 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P {$<$} 0.001, R2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.},
  journal = {Nature Medicine},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC5345907},
  pmid = {28112736}
}

@article{claessonGutMicrobiotaComposition2012,
  title = {Gut Microbiota Composition Correlates with Diet and Health in the Elderly},
  author = {Claesson, Marcus J. and Jeffery, Ian B. and Conde, Susana and Power, Susan E. and O'Connor, Eibhl{\'i}s M. and Cusack, Siobh{\'a}n and Harris, Hugh M. B. and Coakley, Mairead and Lakshminarayanan, Bhuvaneswari and O'Sullivan, Orla and Fitzgerald, Gerald F. and Deane, Jennifer and O'Connor, Michael and Harnedy, Norma and O'Connor, Kieran and O'Mahony, Denis and {van Sinderen}, Douwe and Wallace, Martina and Brennan, Lorraine and Stanton, Catherine and Marchesi, Julian R. and Fitzgerald, Anthony P. and Shanahan, Fergus and Hill, Colin and Ross, R. Paul and O'Toole, Paul W.},
  year = {2012},
  month = aug,
  volume = {488},
  pages = {178--184},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature11319},
  abstract = {Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.},
  copyright = {2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7410}
}

@article{clarkCulturingAnaerobes2019,
  title = {Culturing Anaerobes},
  author = {Clark, Hannah},
  year = {2019},
  month = jun,
  doi = {10.1038/d42859-019-00007-1},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  language = {en}
}

@article{claytonPharmacometabonomicIdentificationSignificant2009,
  title = {Pharmacometabonomic Identification of a Significant Host-Microbiome Metabolic Interaction Affecting Human Drug Metabolism},
  author = {Clayton, T. Andrew and Baker, David and Lindon, John C. and Everett, Jeremy R. and Nicholson, Jeremy K.},
  year = {2009},
  month = aug,
  volume = {106},
  pages = {14728--14733},
  issn = {1091-6490},
  doi = {10.1073/pnas.0904489106},
  abstract = {We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by (1)H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {Acetaminophen,Administration; Oral,Adolescent,Adult,Analgesics; Non-Narcotic,Bacteria,Cresols,Gastrointestinal Tract,Host-Pathogen Interactions,Humans,Magnetic Resonance Spectroscopy,Male,Middle Aged,Sulfates,Sulfuric Acid Esters,Young Adult,药物代谢,里程碑},
  language = {eng},
  number = {34},
  pmcid = {PMC2731842},
  pmid = {19667173}
}

@article{costelloBacterialCommunityVariation2009,
  title = {Bacterial Community Variation in Human Body Habitats across Space and Time},
  author = {Costello, Elizabeth K. and Lauber, Christian L. and Hamady, Micah and Fierer, Noah and Gordon, Jeffrey I. and Knight, Rob},
  year = {2009},
  month = dec,
  volume = {326},
  pages = {1694--1697},
  issn = {1095-9203},
  doi = {10.1126/science.1177486},
  abstract = {Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.},
  journal = {Science (New York, N.Y.)},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {5960},
  pmcid = {PMC3602444},
  pmid = {19892944}
}

@article{davidDietRapidlyReproducibly2014,
  title = {Diet Rapidly and Reproducibly Alters the Human Gut Microbiome},
  author = {David, Lawrence A. and Maurice, Corinne F. and Carmody, Rachel N. and Gootenberg, David B. and Button, Julie E. and Wolfe, Benjamin E. and Ling, Alisha V. and Devlin, A. Sloan and Varma, Yug and Fischbach, Michael A. and Biddinger, Sudha B. and Dutton, Rachel J. and Turnbaugh, Peter J.},
  year = {2014},
  month = jan,
  volume = {505},
  pages = {559--563},
  issn = {0028-0836},
  doi = {10.1038/nature12820},
  abstract = {Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.},
  copyright = {\textcopyright{} 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  file = {E\:\\zotero.storage.2016\\Nature\\2014\\DavidL et al_Nature_2014.pdf},
  journal = {Nature},
  language = {en},
  number = {7484}
}

@article{desaiDietaryFiberDeprivedGut2016,
  title = {A {{Dietary Fiber}}-{{Deprived Gut Microbiota Degrades}} the {{Colonic Mucus Barrier}} and {{Enhances Pathogen Susceptibility}}},
  author = {Desai, Mahesh S. and Seekatz, Anna M. and Koropatkin, Nicole M. and Kamada, Nobuhiko and Hickey, Christina A. and Wolter, Mathis and Pudlo, Nicholas A. and Kitamoto, Sho and Terrapon, Nicolas and Muller, Arnaud and Young, Vincent B. and Henrissat, Bernard and Wilmes, Paul and Stappenbeck, Thaddeus S. and N{\'u}{\~n}ez, Gabriel and Martens, Eric C.},
  year = {2016},
  month = nov,
  volume = {167},
  pages = {1339-1353.e21},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2016.10.043},
  abstract = {Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.},
  journal = {Cell},
  keywords = {喂养菌群,里程碑},
  language = {eng},
  number = {5},
  pmcid = {PMC5131798},
  pmid = {27863247}
}

@article{digiulioTemporalSpatialVariation2015,
  title = {Temporal and Spatial Variation of the Human Microbiota during Pregnancy},
  author = {DiGiulio, Daniel B. and Callahan, Benjamin J. and McMurdie, Paul J. and Costello, Elizabeth K. and Lyell, Deirdre J. and Robaczewska, Anna and Sun, Christine L. and Goltsman, Daniela S. A. and Wong, Ronald J. and Shaw, Gary and Stevenson, David K. and Holmes, Susan P. and Relman, David A.},
  year = {2015},
  month = sep,
  volume = {112},
  pages = {11060--11065},
  issn = {1091-6490},
  doi = {10.1073/pnas.1502875112},
  abstract = {Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P {$>$} 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {35},
  pmcid = {PMC4568272},
  pmid = {26283357}
}

@article{dioneQuasiuniversalMediumBreak2016,
  title = {A Quasi-Universal Medium to Break the Aerobic/Anaerobic Bacterial Culture Dichotomy in Clinical Microbiology},
  author = {Dione, N. and Khelaifia, S. and La Scola, B. and Lagier, J. C. and Raoult, D.},
  year = {2016},
  month = jan,
  volume = {22},
  pages = {53--58},
  issn = {1469-0691},
  doi = {10.1016/j.cmi.2015.10.032},
  abstract = {In the mid-19th century, the dichotomy between aerobic and anaerobic bacteria was introduced. Nevertheless, the aerobic growth of strictly anaerobic bacterial species such as Ruminococcus gnavus and Fusobacterium necrophorum, in a culture medium containing antioxidants, was recently demonstrated. We tested aerobically the culture of 623 bacterial strains from 276 bacterial species including 82 strictly anaerobic, 154 facultative anaerobic, 31 aerobic and nine microaerophilic bacterial species as well as ten fungi. The basic culture medium was based on Schaedler agar supplemented with 1 g/L ascorbic acid and 0.1 g/L glutathione (R-medium). We successively optimized this media, adding 0.4 g/L uric acid, using separate autoclaving of the component, or adding haemin 0.1 g/L or {$\alpha$}-ketoglutarate 2 g/L. In the basic medium, 237 bacterial species and ten fungal species grew but with no growth of 36 bacterial species, including 22 strict anaerobes. Adding uric acid allowed the growth of 14 further species including eight strict anaerobes, while separate autoclaving allowed the growth of all tested bacterial strains. To extend its potential use for fastidious bacteria, we added haemin for Haemophilus influenzae, Haemophilus parainfluenzae and Eikenella corrodens and {$\alpha$}-ketoglutarate for Legionella pneumophila. This medium allowed the growth of all tested strains with the exception of Mycobacterium tuberculosis and Mycobacterium bovis. Testing primoculture and more fastidious species will constitute the main work to be done, but R-medium coupled with a rapid identification method (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) will facilitate the anaerobic culture in clinical microbiology laboratories.},
  journal = {Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases},
  keywords = {Anaerobes,antioxidant,ascorbic acid,Bacteria; Aerobic,Bacteria; Anaerobic,Bacterial Infections,Bacteriological Techniques,Culture Media,glutathione,Humans,uric acid,培养组学,里程碑},
  language = {eng},
  number = {1},
  pmid = {26577141}
}

@article{dominguez-belloDeliveryModeShapes2010,
  title = {Delivery Mode Shapes the Acquisition and Structure of the Initial Microbiota across Multiple Body Habitats in Newborns},
  author = {{Dominguez-Bello}, Maria G. and Costello, Elizabeth K. and Contreras, Monica and Magris, Magda and Hidalgo, Glida and Fierer, Noah and Knight, Rob},
  year = {2010},
  month = jun,
  volume = {107},
  pages = {11971--11975},
  issn = {1091-6490},
  doi = {10.1073/pnas.1002601107},
  abstract = {Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled {$<$}5 min, and meconium {$<$}24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {26},
  pmcid = {PMC2900693},
  pmid = {20566857}
}

@article{dominguez-belloPartialRestorationMicrobiota2016,
  title = {Partial Restoration of the Microbiota of Cesarean-Born Infants via Vaginal Microbial Transfer},
  author = {{Dominguez-Bello}, Maria G. and {De Jesus-Laboy}, Kassandra M. and Shen, Nan and Cox, Laura M. and Amir, Amnon and Gonzalez, Antonio and Bokulich, Nicholas A. and Song, Se Jin and Hoashi, Marina and {Rivera-Vinas}, Juana I. and Mendez, Keimari and Knight, Rob and Clemente, Jose C.},
  year = {2016},
  month = mar,
  volume = {22},
  pages = {250--253},
  issn = {1546-170X},
  doi = {10.1038/nm.4039},
  abstract = {Exposure of newborns to the maternal vaginal microbiota is interrupted with cesarean birthing. Babies delivered by cesarean section (C-section) acquire a microbiota that differs from that of vaginally delivered infants, and C-section delivery has been associated with increased risk for immune and metabolic disorders. Here we conducted a pilot study in which infants delivered by C-section were exposed to maternal vaginal fluids at birth. Similarly to vaginally delivered babies, the gut, oral and skin bacterial communities of these newborns during the first 30 d of life was enriched in vaginal bacteria--which were underrepresented in unexposed C-section-delivered infants--and the microbiome similarity to those of vaginally delivered infants was greater in oral and skin samples than in anal samples. Although the long-term health consequences of restoring the microbiota of C-section-delivered infants remain unclear, our results demonstrate that vaginal microbes can be partially restored at birth in C-section-delivered babies.},
  journal = {Nature Medicine},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC5062956},
  pmid = {26828196}
}

@article{durgandavidj.RoleGutMicrobiome2016,
  title = {Role of the {{Gut Microbiome}} in {{Obstructive Sleep Apnea}}\textendash{{Induced Hypertension}}},
  author = {{Durgan David J.} and {Ganesh Bhanu P.} and {Cope Julia L.} and {Ajami Nadim J.} and {Phillips Sharon C.} and {Petrosino Joseph F.} and {Hollister Emily B.} and {Bryan Robert M.}},
  year = {2016},
  month = feb,
  volume = {67},
  pages = {469--474},
  publisher = {{American Heart Association}},
  doi = {10.1161/HYPERTENSIONAHA.115.06672},
  abstract = {Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (P{$<$}0.05 each). Bacterial community characterization was performed on fecal pellets isolated before and after 14 days of OSA in chow and high-fat fed rats. High-fat diet and OSA led to significant alterations of the gut microbiota, including decreases in bacterial taxa known to produce the short chain fatty acid butyrate (P{$<$}0.05). Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; P{$<$}0.05). These studies demonstrate a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension.},
  journal = {Hypertension},
  number = {2}
}

@article{earleQuantitativeImagingGut2015,
  title = {Quantitative {{Imaging}} of {{Gut Microbiota Spatial Organization}}},
  author = {Earle, Kristen A. and Billings, Gabriel and Sigal, Michael and Lichtman, Joshua S. and Hansson, Gunnar C. and Elias, Joshua E. and Amieva, Manuel R. and Huang, Kerwyn Casey and Sonnenburg, Justin L.},
  year = {2015},
  month = oct,
  volume = {18},
  pages = {478--488},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.09.002},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {4}
}

@article{eckburgDiversityHumanIntestinal2005,
  title = {Diversity of the {{Human Intestinal Microbial Flora}}},
  author = {Eckburg, Paul B. and Bik, Elisabeth M. and Bernstein, Charles N. and Purdom, Elizabeth and Dethlefsen, Les and Sargent, Michael and Gill, Steven R. and Nelson, Karen E. and Relman, David A.},
  year = {2005},
  month = jun,
  volume = {308},
  pages = {1635--1638},
  issn = {0036-8075},
  doi = {10.1126/science.1110591},
  abstract = {The human endogenous intestinal microflora is an essential ``organ'' in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.},
  journal = {Science (New York, N.Y.)},
  keywords = {菌群稳定性,里程碑},
  number = {5728},
  pmcid = {PMC1395357},
  pmid = {15831718}
}

@article{everardCrosstalkAkkermansiaMuciniphila2013,
  title = {Cross-Talk between {{Akkermansia}} Muciniphila and Intestinal Epithelium Controls Diet-Induced Obesity},
  author = {Everard, Amandine and Belzer, Clara and Geurts, Lucie and Ouwerkerk, Janneke P. and Druart, C{\'e}line and Bindels, Laure B. and Guiot, Yves and Derrien, Muriel and Muccioli, Giulio G. and Delzenne, Nathalie M. and de Vos, Willem M. and Cani, Patrice D.},
  year = {2013},
  month = may,
  volume = {110},
  pages = {9066--9071},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.1219451110},
  abstract = {Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.},
  chapter = {Biological Sciences},
  copyright = {\textcopyright{}  . Freely available online through the PNAS open access option.},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {22},
  pmid = {23671105}
}

@article{everardResponsesGutMicrobiota2011,
  title = {Responses of {{Gut Microbiota}} and {{Glucose}} and {{Lipid Metabolism}} to {{Prebiotics}} in {{Genetic Obese}} and {{Diet}}-{{Induced Leptin}}-{{Resistant Mice}}},
  author = {Everard, Amandine and Lazarevic, Vladimir and Derrien, Muriel and Girard, Myriam and Muccioli, Giulio G. and Neyrinck, Audrey M. and Possemiers, Sam and Holle, Ann Van and Fran{\c c}ois, Patrice and de Vos, Willem M. and Delzenne, Nathalie M. and Schrenzel, Jacques and Cani, Patrice D.},
  year = {2011},
  month = nov,
  volume = {60},
  pages = {2775--2786},
  publisher = {{American Diabetes Association}},
  issn = {0012-1797, 1939-327X},
  doi = {10.2337/db11-0227},
  abstract = {OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a {$>$}10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat\textendash fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.},
  chapter = {Metabolism},
  copyright = {\textcopyright{} 2011 by the American Diabetes Association.. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.},
  journal = {Diabetes},
  language = {en},
  number = {11},
  pmid = {21933985}
}

@article{faithLongtermStabilityHuman2013,
  title = {The Long-Term Stability of the Human Gut Microbiota},
  author = {Faith, Jeremiah J. and Guruge, Janaki L. and Charbonneau, Mark and Subramanian, Sathish and Seedorf, Henning and Goodman, Andrew L. and Clemente, Jose C. and Knight, Rob and Heath, Andrew C. and Leibel, Rudolph L. and Rosenbaum, Michael and Gordon, Jeffrey I.},
  year = {2013},
  month = jul,
  volume = {341},
  pages = {1237439},
  issn = {1095-9203},
  doi = {10.1126/science.1237439},
  abstract = {A low-error 16S ribosomal RNA amplicon sequencing method, in combination with whole-genome sequencing of {$>$}500 cultured isolates, was used to characterize bacterial strain composition in the fecal microbiota of 37 U.S. adults sampled for up to 5 years. Microbiota stability followed a power-law function, which when extrapolated suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members but not from unrelated individuals. Sampling of individuals who consumed a monotonous liquid diet for up to 32 weeks indicated that changes in strain composition were better predicted by changes in weight than by differences in sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target.},
  journal = {Science (New York, N.Y.)},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {6141},
  pmcid = {PMC3791589},
  pmid = {23828941}
}

@article{falonyPopulationlevelAnalysisGut2016,
  title = {Population-Level Analysis of Gut Microbiome Variation},
  author = {Falony, G. and Joossens, M. and {Vieira-Silva}, S. and Wang, J. and Darzi, Y. and Faust, K. and Kurilshikov, A. and Bonder, M. J. and {Valles-Colomer}, M. and Vandeputte, D. and Tito, R. Y. and Chaffron, S. and Rymenans, L. and Verspecht, C. and De Sutter, L. and {Lima-Mendez}, G. and Dhoe, K. and Jonckheere, K. and Homola, D. and Garcia, R. and Tigchelaar, E. F. and Eeckhaudt, L. and Fu, J. and Henckaerts, L. and Zhernakova, A. and Wijmenga, C. and Raes, J.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {560--564},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad3503},
  abstract = {``Normal'' for the gut microbiota For the benefit of future clinical studies, it is critical to establish what constitutes a ``normal'' gut microbiome, if it exists at all. Through fecal samples and questionnaires, Falony et al. and Zhernakova et al. targeted general populations in Belgium and the Netherlands, respectively. Gut microbiota composition correlated with a range of factors including diet, use of medication, red blood cell counts, fecal chromogranin A, and stool consistency. The data give some hints for possible biomarkers of normal gut communities. Science, this issue pp. 560 and 565 Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92\% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design. Two large-scale studies in Western Europe establish environment-diet-microbe-host interactions. Two large-scale studies in Western Europe establish environment-diet-microbe-host interactions.},
  file = {E\:\\zotero.storage.2016\\Science\\2016\\2016_Population-level analysis of gut microbiome variation.pdf},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{farrellImportanceFeedingYour2019,
  title = {The Importance of Feeding Your Microbiota},
  author = {Farrell, Alison},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00015-1},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  keywords = {喂养菌群,里程碑},
  language = {en}
}

@article{ferrettiMothertoInfantMicrobialTransmission2018,
  title = {Mother-to-{{Infant Microbial Transmission}} from {{Different Body Sites Shapes}} the {{Developing Infant Gut Microbiome}}},
  author = {Ferretti, Pamela and Pasolli, Edoardo and Tett, Adrian and Asnicar, Francesco and Gorfer, Valentina and Fedi, Sabina and Armanini, Federica and Truong, Duy Tin and Manara, Serena and Zolfo, Moreno and Beghini, Francesco and Bertorelli, Roberto and De Sanctis, Veronica and Bariletti, Ilaria and Canto, Rosarita and Clementi, Rosanna and Cologna, Marina and Crif{\`o}, Tiziana and Cusumano, Giuseppina and Gottardi, Stefania and Innamorati, Claudia and Mas{\`e}, Caterina and Postai, Daniela and Savoi, Daniela and Duranti, Sabrina and Lugli, Gabriele Andrea and Mancabelli, Leonardo and Turroni, Francesca and Ferrario, Chiara and Milani, Christian and Mangifesta, Marta and Anzalone, Rosaria and Viappiani, Alice and Yassour, Moran and Vlamakis, Hera and Xavier, Ramnik and Collado, Carmen Maria and Koren, Omry and Tateo, Saverio and Soffiati, Massimo and Pedrotti, Anna and Ventura, Marco and Huttenhower, Curtis and Bork, Peer and Segata, Nicola},
  year = {2018},
  month = nov,
  volume = {24},
  pages = {133-145.e5},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2018.06.005},
  abstract = {The acquisition and development of the infant microbiome are key to establishing a healthy host-microbiome symbiosis. The maternal microbial reservoir is thought to play a crucial role in this process. However, the source and transmission routes of the infant pioneering microbes are poorly understood. To address this, we longitudinally sampled the microbiome of 25 mother-infant pairs~across multiple body sites from birth up to 4~months postpartum. Strain-level metagenomic profiling showed a rapid influx of microbes at birth~followed by strong selection during the first few days of life. Maternal skin and vaginal strains~colonize only transiently, and the infant continues to acquire microbes from distinct maternal sources after birth. Maternal gut strains proved more persistent in the infant gut and ecologically better adapted than those acquired from other sources. Together, these data describe the mother-to-infant microbiome transmission routes that are integral in the development of the infant microbiome.},
  journal = {Cell Host \& Microbe},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {1},
  pmcid = {PMC6716579},
  pmid = {30001516}
}

@article{filippoImpactDietShaping2010,
  title = {Impact of Diet in Shaping Gut Microbiota Revealed by a Comparative Study in Children from {{Europe}} and Rural {{Africa}}},
  author = {Filippo, Carlotta De and Cavalieri, Duccio and Paola, Monica Di and Ramazzotti, Matteo and Poullet, Jean Baptiste and Massart, Sebastien and Collini, Silvia and Pieraccini, Giuseppe and Lionetti, Paolo},
  year = {2010},
  month = aug,
  volume = {107},
  pages = {14691--14696},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.1005963107},
  abstract = {Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural African village of Burkina Faso (BF), where the diet, high in fiber content, is similar to that of early human settlements at the time of the birth of agriculture. By using high-throughput 16S rDNA sequencing and biochemical analyses, we found significant differences in gut microbiota between the two groups. BF children showed a significant enrichment in Bacteroidetes and depletion in Firmicutes (P {$<$} 0.001), with a unique abundance of bacteria from the genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for cellulose and xylan hydrolysis, completely lacking in the EU children. In addition, we found significantly more short-chain fatty acids (P {$<$} 0.001) in BF than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were significantly underrepresented in BF than in EU children (P {$<$} 0.05). We hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF individuals, allowing them to maximize energy intake from fibers while also protecting them from inflammations and noninfectious colonic diseases. This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide.},
  chapter = {Biological Sciences},
  copyright = {\textcopyright{}  . Freely available online through the PNAS open access option.},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {33},
  pmid = {20679230}
}

@article{forslundDisentanglingTypeDiabetes2015a,
  title = {Disentangling Type 2 Diabetes and Metformin Treatment Signatures in the Human Gut Microbiota},
  author = {Forslund, Kristoffer and Hildebrand, Falk and Nielsen, Trine and Falony, Gwen and Le Chatelier, Emmanuelle and Sunagawa, Shinichi and Prifti, Edi and {Vieira-Silva}, Sara and Gudmundsdottir, Valborg and Krogh Pedersen, Helle and Arumugam, Manimozhiyan and Kristiansen, Karsten and Yvonne Voigt, Anita and Vestergaard, Henrik and Hercog, Rajna and Igor Costea, Paul and Roat Kultima, Jens and Li, Junhua and J{\o}rgensen, Torben and Levenez, Florence and Dore, Jo{\"e}l and Bj{\o}rn Nielsen, H. and Brunak, S{\o}ren and Raes, Jeroen and Hansen, Torben and Wang, Jun and Dusko Ehrlich, S. and Bork, Peer and Pedersen, Oluf},
  year = {2015},
  month = dec,
  volume = {528},
  pages = {262--266},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature15766},
  abstract = {Growing evidence from metagenome-wide association studies link multiple common disorders to microbial dysbiosis but effects of drug treatment are often not accounted for; here, the authors re-analyse two previous metagenomic studies of type 2 diabetes mellitus patients together with a novel cohort to determine the effects of the widely prescribed antidiabetic drug metformin and highlight the need to distinguish the effects of a disease from the effects of treatment on the gut microbiota.},
  copyright = {2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7581}
}

@article{frankMolecularphylogeneticCharacterizationMicrobial2007,
  title = {Molecular-Phylogenetic Characterization of Microbial Community Imbalances in Human Inflammatory Bowel Diseases},
  author = {Frank, Daniel N. and Amand, Allison L. St and Feldman, Robert A. and Boedeker, Edgar C. and Harpaz, Noam and Pace, Norman R.},
  year = {2007},
  month = aug,
  volume = {104},
  pages = {13780--13785},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.0706625104},
  abstract = {The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.},
  chapter = {Biological Sciences},
  copyright = {\textcopyright{} 2007 by The National Academy of Sciences of the USA},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {34},
  pmid = {17699621}
}

@article{fredricksMolecularIdentificationBacteria2005,
  title = {Molecular Identification of Bacteria Associated with Bacterial Vaginosis},
  author = {Fredricks, David N. and Fiedler, Tina L. and Marrazzo, Jeanne M.},
  year = {2005},
  month = nov,
  volume = {353},
  pages = {1899--1911},
  issn = {1533-4406},
  doi = {10.1056/NEJMoa043802},
  abstract = {BACKGROUND: Bacterial vaginosis affects millions of women and is associated with several serious health conditions. The cause of bacterial vaginosis remains poorly understood despite numerous studies based on cultures. Bacteria in microbial communities can be identified without cultivation by characterizing their ribosomal DNA (rDNA) sequences. METHODS: We identified bacteria in samples of vaginal fluid with a combination of broad-range polymerase-chain-reaction (PCR) amplification of 16S rDNA with clone analysis, bacterium-specific PCR assay of 16S rDNA, and fluorescence in situ hybridization (FISH) performed directly on vaginal fluid from 27 subjects with bacterial vaginosis and 46 without the condition. Twenty-one subjects were studied with the use of broad-range PCR of 16S rDNA, and 73 subjects were studied with the use of bacterium-specific PCR. RESULTS: Women without bacterial vaginosis had 1 to 6 vaginal bacterial species (phylotypes) in each sample (mean, 3.3), as detected by broad-range PCR of 16S rDNA, and lactobacillus species were the predominant bacteria noted (83 to 100 percent of clones). Women with bacterial vaginosis had greater bacterial diversity (P{$<$}0.001), with 9 to 17 phylotypes (mean, 12.6) detected per sample and newly recognized species present in 32 to 89 percent of clones per sample library (mean, 58 percent). Thirty-five unique bacterial species were detected in the women with bacterial vaginosis, including several species with no close cultivated relatives. Bacterium-specific PCR assays showed that several bacteria that had not been previously described were highly prevalent in subjects with bacterial vaginosis but rare in healthy controls. FISH confirmed that newly recognized bacteria detected by PCR corresponded to specific bacterial morphotypes visible in vaginal fluid. CONCLUSIONS: Women with bacterial vaginosis have complex vaginal infections with many newly recognized species, including three bacteria in the Clostridiales order that were highly specific for bacterial vaginosis.},
  journal = {The New England Journal of Medicine},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {18},
  pmid = {16267321}
}

@article{fujimuraMicrobiotaAllergyAsthma2015,
  title = {Microbiota in {{Allergy}} and {{Asthma}} and the {{Emerging Relationship}} with the {{Gut Microbiome}}},
  author = {Fujimura, Kei E. and Lynch, Susan V.},
  year = {2015},
  month = may,
  volume = {17},
  pages = {592--602},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.04.007},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{furetDifferentialAdaptationHuman2010,
  title = {Differential {{Adaptation}} of {{Human Gut Microbiota}} to {{Bariatric Surgery}}\textendash{{Induced Weight Loss}}: {{Links With Metabolic}} and {{Low}}-{{Grade Inflammation Markers}}},
  shorttitle = {Differential {{Adaptation}} of {{Human Gut Microbiota}} to {{Bariatric Surgery}}\textendash{{Induced Weight Loss}}},
  author = {Furet, Jean-Pierre and Kong, Ling-Chun and Tap, Julien and Poitou, Christine and Basdevant, Arnaud and Bouillot, Jean-Luc and Mariat, Denis and Corthier, G{\'e}rard and Dor{\'e}, Jo{\"e}l and Henegar, Corneliu and Rizkalla, Salwa and Cl{\'e}ment, Karine},
  year = {2010},
  month = dec,
  volume = {59},
  pages = {3049--3057},
  publisher = {{American Diabetes Association}},
  issn = {0012-1797, 1939-327X},
  doi = {10.2337/db10-0253},
  abstract = {OBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at M0 and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at M0 and throughout the follow-up after surgery independently of changes in food intake. CONCLUSIONS These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake.},
  chapter = {Obesity Studies},
  copyright = {\textcopyright{} 2010 by the American Diabetes Association..  Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.},
  journal = {Diabetes},
  language = {en},
  number = {12},
  pmid = {20876719}
}

@article{gajerTemporalDynamicsHuman2012,
  title = {Temporal Dynamics of the Human Vaginal Microbiota},
  author = {Gajer, Pawel and Brotman, Rebecca M. and Bai, Guoyun and Sakamoto, Joyce and Sch{\"u}tte, Ursel M. E. and Zhong, Xue and Koenig, Sara S. K. and Fu, Li and Ma, Zhanshan Sam and Zhou, Xia and Abdo, Zaid and Forney, Larry J. and Ravel, Jacques},
  year = {2012},
  month = may,
  volume = {4},
  pages = {132ra52},
  issn = {1946-6242},
  doi = {10.1126/scitranslmed.3003605},
  abstract = {Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.},
  journal = {Science Translational Medicine},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {132},
  pmcid = {PMC3722878},
  pmid = {22553250}
}

@article{gaoMolecularAnalysisHuman2007,
  title = {Molecular Analysis of Human Forearm Superficial Skin Bacterial Biota},
  author = {Gao, Zhan and Tseng, Chi-hong and Pei, Zhiheng and Blaser, Martin J.},
  year = {2007},
  month = feb,
  volume = {104},
  pages = {2927--2932},
  issn = {0027-8424},
  doi = {10.1073/pnas.0607077104},
  abstract = {The microbial ecology of human skin is complex, but little is known about its species composition. We examined the diversity of the skin biota from the superficial volar left and right forearms in six healthy subjects using broad-range small subunit rRNA genes (16S rDNA) PCR-based sequencing of randomly selected clones. For the initial 1,221 clones analyzed, 182 species-level operational taxonomic units (SLOTUs) belonging to eight phyla were identified, estimated as 74.0\% [95\% confidence interval (C.I.), approximately 64.8-77.9\%] of the SLOTUs in this ecosystem; 48.0 +/- 12.2 SLOTUs were found in each subject. Three phyla (Actinobacteria, Firmicutes, and Proteobacteria) accounted for 94.6\% of the clones. Most (85.3\%) of the bacterial sequences corresponded to known and cultivated species, but 98 (8.0\%) clones, comprising 30 phylotypes, had {$<$}97\% similarity to prior database sequences. Only 6 (6.6\%) of the 91 genera and 4 (2.2\%) of the 182 SLOTUs, respectively, were found in all six subjects. Analysis of 817 clones obtained 8-10 months later from four subjects showed additional phyla (numbering 2), genera (numbering 28), and SLOTUs (numbering 65). Only four (3.4\%) of the 119 genera (Propionibacteria, Corynebacteria, Staphylococcus, and Streptococcus) were observed in each subject tested twice, but these genera represented 54.4\% of all clones. These results show that the bacterial biota in normal superficial skin is highly diverse, with few well conserved and well represented genera, but otherwise low-level interpersonal consensus.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {8},
  pmcid = {PMC1815283},
  pmid = {17293459}
}

@article{gensollenHowColonizationMicrobiota2016,
  title = {How Colonization by Microbiota in Early Life Shapes the Immune System},
  author = {Gensollen, T. and Iyer, S. S. and Kasper, D. L. and Blumberg, R. S.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {539--544},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad9378},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{geversTreatmentNaiveMicrobiomeNewOnset2014,
  title = {The {{Treatment}}-{{Naive Microbiome}} in {{New}}-{{Onset Crohn}}'s {{Disease}}},
  author = {Gevers, Dirk and Kugathasan, Subra and Denson, Lee A. and {V{\'a}zquez-Baeza}, Yoshiki and Van Treuren, Will and Ren, Boyu and Schwager, Emma and Knights, Dan and Song, Se Jin and Yassour, Moran and Morgan, Xochitl C. and Kostic, Aleksandar D. and Luo, Chengwei and Gonz{\'a}lez, Antonio and McDonald, Daniel and Haberman, Yael and Walters, Thomas and Baker, Susan and Rosh, Joel and Stephens, Michael and Heyman, Melvin and Markowitz, James and Baldassano, Robert and Griffiths, Anne and Sylvester, Francisco and Mack, David and Kim, Sandra and Crandall, Wallace and Hyams, Jeffrey and Huttenhower, Curtis and Knight, Rob and Xavier, Ramnik J.},
  year = {2014},
  month = mar,
  volume = {15},
  pages = {382--392},
  publisher = {{Elsevier}},
  issn = {1931-3128},
  doi = {10.1016/j.chom.2014.02.005},
  journal = {Cell Host \& Microbe},
  language = {English},
  number = {3},
  pmid = {24629344}
}

@article{ghannoumCharacterizationOralFungal2010,
  title = {Characterization of the Oral Fungal Microbiome (Mycobiome) in Healthy Individuals},
  author = {Ghannoum, Mahmoud A. and Jurevic, Richard J. and Mukherjee, Pranab K. and Cui, Fan and Sikaroodi, Masoumeh and Naqvi, Ammar and Gillevet, Patrick M.},
  year = {2010},
  month = jan,
  volume = {6},
  pages = {e1000713},
  issn = {1553-7374},
  doi = {10.1371/journal.ppat.1000713},
  abstract = {The oral microbiome-organisms residing in the oral cavity and their collective genome-are critical components of health and disease. The fungal component of the oral microbiota has not been characterized. In this study, we used a novel multitag pyrosequencing approach to characterize fungi present in the oral cavity of 20 healthy individuals, using the pan-fungal internal transcribed spacer (ITS) primers. Our results revealed the "basal" oral mycobiome profile of the enrolled individuals, and showed that across all the samples studied, the oral cavity contained 74 culturable and 11 non-culturable fungal genera. Among these genera, 39 were present in only one person, 16 genera were present in two participants, and 5 genera were present in three people, while 15 genera (including non-culturable organisms) were present in {$>$}/=4 (20\%) participants. Candida species were the most frequent (isolated from 75\% of participants), followed by Cladosporium (65\%), Aureobasidium, Saccharomycetales (50\% for both), Aspergillus (35\%), Fusarium (30\%), and Cryptococcus (20\%). Four of these predominant genera are known to be pathogenic in humans. The low-abundance genera may represent environmental fungi present in the oral cavity and could simply be spores inhaled from the air or material ingested with food. Among the culturable genera, 61 were represented by one species each, while 13 genera comprised between 2 and 6 different species; the total number of species identified were 101. The number of species in the oral cavity of each individual ranged between 9 and 23. Principal component (PCO) analysis of the obtained data set followed by sample clustering and UniFrac analysis revealed that White males and Asian males clustered differently from each other, whereas both Asian and White females clustered together. This is the first study that identified the "basal mycobiome" of healthy individuals, and provides the basis for a detailed characterization of the oral mycobiome in health and disease.},
  journal = {PLoS pathogens},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {1},
  pmcid = {PMC2795202},
  pmid = {20072605}
}

@article{giongoDefiningAutoimmuneMicrobiome2011,
  title = {Toward Defining the Autoimmune Microbiome for Type 1 Diabetes},
  author = {Giongo, Adriana and Gano, Kelsey A. and Crabb, David B. and Mukherjee, Nabanita and Novelo, Luis L. and Casella, George and Drew, Jennifer C. and Ilonen, Jorma and Knip, Mikael and Hy{\"o}ty, Heikki and Veijola, Riitta and Simell, Tuula and Simell, Olli and Neu, Josef and Wasserfall, Clive H. and Schatz, Desmond and Atkinson, Mark A. and Triplett, Eric W.},
  year = {2011},
  month = jan,
  volume = {5},
  pages = {82--91},
  publisher = {{Nature Publishing Group}},
  issn = {1751-7370},
  doi = {10.1038/ismej.2010.92},
  abstract = {Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24\% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20\% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.},
  copyright = {2011 International Society for Microbial Ecology},
  journal = {The ISME Journal},
  language = {en},
  number = {1}
}

@article{goffauFecalMicrobiotaComposition2013,
  title = {Fecal {{Microbiota Composition Differs Between Children With}} {$\beta$}-{{Cell Autoimmunity}} and {{Those Without}}},
  author = {de Goffau, Marcus C. and Luopaj{\"a}rvi, Kristiina and Knip, Mikael and Ilonen, Jorma and Ruohtula, Terhi and H{\"a}rk{\"o}nen, Taina and Orivuori, Laura and Hakala, Saara and Welling, Gjalt W. and Harmsen, Hermie J. and Vaarala, Outi},
  year = {2013},
  month = apr,
  volume = {62},
  pages = {1238--1244},
  publisher = {{American Diabetes Association}},
  issn = {0012-1797, 1939-327X},
  doi = {10.2337/db12-0526},
  abstract = {The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects. To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing. Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with {$\beta$}-cell autoimmunity. In addition, a dearth of the two most dominant Bifidobacterium species, Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with {$\beta$}-cell autoimmunity. We did not find increased fecal calprotectin or IgA as marker of inflammation in children with {$\beta$}-cell autoimmunity. Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.},
  chapter = {Original Research},
  copyright = {\textcopyright{} 2013 by the American Diabetes Association.. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.},
  journal = {Diabetes},
  language = {en},
  number = {4},
  pmid = {23274889}
}

@article{goodmanExtensivePersonalHuman2011,
  title = {Extensive Personal Human Gut Microbiota Culture Collections Characterized and Manipulated in Gnotobiotic Mice},
  author = {Goodman, Andrew L. and Kallstrom, George and Faith, Jeremiah J. and Reyes, Alejandro and Moore, Aimee and Dantas, Gautam and Gordon, Jeffrey I.},
  year = {2011},
  month = apr,
  volume = {108},
  pages = {6252--6257},
  issn = {1091-6490},
  doi = {10.1073/pnas.1102938108},
  abstract = {The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {Animals,Bacteria,Cell Culture Techniques,Feces,Gastrointestinal Tract,Germ-Free Life,Humans,Metagenome,Mice,Phylogeny,培养组学,里程碑},
  language = {eng},
  number = {15},
  pmcid = {PMC3076821},
  pmid = {21436049}
}

@article{goodrichCrossspeciesComparisonsHost2016,
  title = {Cross-Species Comparisons of Host Genetic Associations with the Microbiome},
  author = {Goodrich, J. K. and Davenport, E. R. and Waters, J. L. and Clark, A. G. and Ley, R. E.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {532--535},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad9379},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{gregoryTransmissionAtherosclerosisSusceptibility2015,
  title = {Transmission of {{Atherosclerosis Susceptibility}} with {{Gut Microbial Transplantation}}},
  author = {Gregory, Jill C. and Buffa, Jennifer A. and Org, Elin and Wang, Zeneng and Levison, Bruce S. and Zhu, Weifei and Wagner, Matthew A. and Bennett, Brian J. and Li, Lin and DiDonato, Joseph A. and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2015},
  month = feb,
  volume = {290},
  pages = {5647--5660},
  publisher = {{American Society for Biochemistry and Molecular Biology}},
  issn = {0021-9258, 1083-351X},
  doi = {10.1074/jbc.M114.618249},
  abstract = {Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.},
  journal = {Journal of Biological Chemistry},
  language = {en},
  number = {9},
  pmid = {25550161}
}

@article{griceTopographicalTemporalDiversity2009,
  title = {Topographical and {{Temporal Diversity}} of the {{Human Skin Microbiome}}},
  author = {Grice, Elizabeth A. and Kong, Heidi H. and Conlan, Sean and Deming, Clayton B. and Davis, Joie and Young, Alice C. and Bouffard, Gerard G. and Blakesley, Robert W. and Murray, Patrick R. and Green, Eric D. and Turner, Maria L. and Segre, Julia A.},
  year = {2009},
  month = may,
  volume = {324},
  pages = {1190--1192},
  issn = {0036-8075},
  doi = {10.1126/science.1171700},
  abstract = {Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.},
  journal = {Science (New York, N.Y.)},
  keywords = {技术进步,里程碑},
  number = {5931},
  pmcid = {PMC2805064},
  pmid = {19478181}
}

@article{griceTopographicalTemporalDiversity2009a,
  title = {Topographical and {{Temporal Diversity}} of the {{Human Skin Microbiome}}},
  author = {Grice, Elizabeth A. and Kong, Heidi H. and Conlan, Sean and Deming, Clayton B. and Davis, Joie and Young, Alice C. and Bouffard, Gerard G. and Blakesley, Robert W. and Murray, Patrick R. and Green, Eric D. and Turner, Maria L. and Segre, Julia A.},
  year = {2009},
  month = may,
  volume = {324},
  pages = {1190--1192},
  issn = {0036-8075},
  doi = {10.1126/science.1171700},
  abstract = {Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.},
  journal = {Science (New York, N.Y.)},
  keywords = {菌群稳定性,里程碑},
  number = {5931},
  pmcid = {PMC2805064},
  pmid = {19478181}
}

@article{haiserPredictingManipulatingCardiac2013,
  title = {Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium {{Eggerthella}} Lenta},
  author = {Haiser, Henry J. and Gootenberg, David B. and Chatman, Kelly and Sirasani, Gopal and Balskus, Emily P. and Turnbaugh, Peter J.},
  year = {2013},
  month = jul,
  volume = {341},
  pages = {295--298},
  issn = {1095-9203},
  doi = {10.1126/science.1235872},
  abstract = {Despite numerous examples of the effects of the human gastrointestinal microbiome on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the cardiac drug digoxin by the gut Actinobacterium Eggerthella lenta. Transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome. Pharmacokinetic studies using gnotobiotic mice revealed that dietary protein reduces the in vivo microbial metabolism of digoxin, with significant changes to drug concentration in the serum and urine. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes.},
  journal = {Science (New York, N.Y.)},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {6143},
  pmcid = {PMC3736355},
  pmid = {23869020}
}

@article{hallCommensalDNALimits2008,
  title = {Commensal {{DNA}} Limits Regulatory {{T}} Cell Conversion and Is a Natural Adjuvant of Intestinal Immune Responses},
  author = {Hall, Jason A. and Bouladoux, Nicolas and Sun, Cheng Ming and Wohlfert, Elizabeth A. and Blank, Rebecca B. and Zhu, Qing and Grigg, Michael E. and Berzofsky, Jay A. and Belkaid, Yasmine},
  year = {2008},
  month = oct,
  volume = {29},
  pages = {637--649},
  issn = {1097-4180},
  doi = {10.1016/j.immuni.2008.08.009},
  abstract = {The intestinal tract is in intimate contact with the commensal microflora. Nevertheless, how commensals communicate with cells to ensure immune homeostasis is still unclear. In this study, we found that gut flora DNA (gfDNA) plays a major role in intestinal homeostasis through Toll-like receptor 9 (TLR9) engagement. Tlr9(-/-) mice displayed increased frequencies of CD4(+)Foxp3(+) regulatory T (Treg) cells within intestinal effector sites and reduced constitutive IL-17- and IFN-gamma-producing effector T (Teff) cells. Complementing this, gfDNA limited lamina propria dendritic cell-induced Treg cell conversion in vitro. Further, Treg/Teff cell disequilibrium in Tlr9(-/-) mice led to impaired immune responses to oral infection and to oral vaccination. Impaired intestinal immune responses were recapitulated in mice treated with antibiotics and were reversible after reconstitution with gfDNA. Together, these data point to gfDNA as a natural adjuvant for priming intestinal responses via modulation of Treg/Teff cell equilibrium.},
  journal = {Immunity},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {4},
  pmcid = {PMC2712925},
  pmid = {18835196}
}

@article{hehemannTransferCarbohydrateactiveEnzymes2010,
  title = {Transfer of Carbohydrate-Active Enzymes from Marine Bacteria to {{Japanese}} Gut Microbiota},
  author = {Hehemann, Jan-Hendrik and Correc, Ga{\"e}lle and Barbeyron, Tristan and Helbert, William and Czjzek, Mirjam and Michel, Gurvan},
  year = {2010},
  month = apr,
  volume = {464},
  pages = {908--912},
  issn = {1476-4687},
  doi = {10.1038/nature08937},
  abstract = {Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes, which are absent in the human genome. These enzymes target polysaccharides from terrestrial plants that dominated diet throughout human evolution. The array of CAZymes in gut microbes is highly diverse, exemplified by the human gut symbiont Bacteroides thetaiotaomicron, which contains 261 glycoside hydrolases and polysaccharide lyases, as well as 208 homologues of susC and susD-genes coding for two outer membrane proteins involved in starch utilization. A fundamental question that, to our knowledge, has yet to be addressed is how this diversity evolved by acquiring new genes from microbes living outside the gut. Here we characterize the first porphyranases from a member of the marine Bacteroidetes, Zobellia galactanivorans, active on the sulphated polysaccharide porphyran from marine red algae of the genus Porphyra. Furthermore, we show that genes coding for these porphyranases, agarases and associated proteins have been transferred to the gut bacterium Bacteroides plebeius isolated from Japanese individuals. Our comparative gut metagenome analyses show that porphyranases and agarases are frequent in the Japanese population and that they are absent in metagenome data from North American individuals. Seaweeds make an important contribution to the daily diet in Japan (14.2 g per person per day), and Porphyra spp. (nori) is the most important nutritional seaweed, traditionally used to prepare sushi. This indicates that seaweeds with associated marine bacteria may have been the route by which these novel CAZymes were acquired in human gut bacteria, and that contact with non-sterile food may be a general factor in CAZyme diversity in human gut microbes.},
  journal = {Nature},
  keywords = {喂养菌群,里程碑},
  language = {eng},
  number = {7290},
  pmid = {20376150}
}

@article{holdAssessmentMicrobialDiversity2002,
  title = {Assessment of Microbial Diversity in Human Colonic Samples by {{16S rDNA}} Sequence Analysis},
  author = {Hold, Georgina L. and Pryde, Susan E. and Russell, Valerie J. and Furrie, Elizabeth and Flint, Harry J.},
  year = {2002},
  month = jan,
  volume = {39},
  pages = {33--39},
  issn = {1574-6941},
  doi = {10.1111/j.1574-6941.2002.tb00904.x},
  abstract = {Abstract The bacterial species diversity of three colonic tissue samples from elderly people was investigated by sequence analysis of randomly cloned eubacterial 16S rDNA. The majority of sequences (87\%) clustered within three bacterial groups: (1) Bacteroides; (2) low G+C content Gram-positives related to Clostridium coccoides (cluster XIVa); (3) Gram-positives related to Clostridium leptum (cluster IV). These groups have been shown to dominate the human faecal flora. Only 25\% of sequences were closely related ({$>$}97\%) to current species type strains, and 28\% were less than 97\% related to any database entry. 19\% of sequences were most closely related to recently isolated butyrate-producing bacteria belonging to clusters XIVa and IV, with a further 18\% of the sequences most closely related to Ruminococcus obeum and Ruminococcus torques (members of cluster XIVa). These results provide the first molecular information on the microbial diversity present in human colonic samples.},
  journal = {FEMS microbiology ecology},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {1},
  pmid = {19709182}
}

@article{hooperAngiogeninsNewClass2003,
  title = {Angiogenins: A New Class of Microbicidal Proteins Involved in Innate Immunity},
  shorttitle = {Angiogenins},
  author = {Hooper, Lora V. and Stappenbeck, Thaddeus S. and Hong, Chieu V. and Gordon, Jeffrey I.},
  year = {2003},
  month = mar,
  volume = {4},
  pages = {269--273},
  issn = {1529-2908},
  doi = {10.1038/ni888},
  abstract = {Although angiogenins have been implicated in tumor-associated angiogenesis, their normal physiologic function remains unclear. We show that a previously uncharacterized angiogenin, Ang4, is produced by mouse Paneth cells, is secreted into the gut lumen and has bactericidal activity against intestinal microbes. Ang4 expression is induced by Bacteroides thetaiotaomicron, a predominant member of the gut microflora, revealing a mechanism whereby intestinal commensal bacteria influence gut microbial ecology and shape innate immunity. Furthermore, mouse Ang1 and human angiogenin, circulating proteins induced during inflammation, exhibit microbicidal activity against systemic bacterial and fungal pathogens, suggesting that they contribute to systemic responses to infection. These results establish angiogenins as a family of endogenous antimicrobial proteins.},
  journal = {Nature Immunology},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {3},
  pmid = {12548285}
}

@article{humanmicrobiomejumpstartreferencestrainsconsortiumCatalogReferenceGenomes2010,
  title = {A Catalog of Reference Genomes from the Human Microbiome},
  author = {{Human Microbiome Jumpstart Reference Strains Consortium} and Nelson, Karen E. and Weinstock, George M. and Highlander, Sarah K. and Worley, Kim C. and Creasy, Heather Huot and Wortman, Jennifer Russo and Rusch, Douglas B. and Mitreva, Makedonka and Sodergren, Erica and Chinwalla, Asif T. and Feldgarden, Michael and Gevers, Dirk and Haas, Brian J. and Madupu, Ramana and Ward, Doyle V. and Birren, Bruce W. and Gibbs, Richard A. and Methe, Barbara and Petrosino, Joseph F. and Strausberg, Robert L. and Sutton, Granger G. and White, Owen R. and Wilson, Richard K. and Durkin, Scott and Giglio, Michelle Gwinn and Gujja, Sharvari and Howarth, Clint and Kodira, Chinnappa D. and Kyrpides, Nikos and Mehta, Teena and Muzny, Donna M. and Pearson, Matthew and Pepin, Kymberlie and Pati, Amrita and Qin, Xiang and Yandava, Chandri and Zeng, Qiandong and Zhang, Lan and Berlin, Aaron M. and Chen, Lei and Hepburn, Theresa A. and Johnson, Justin and McCorrison, Jamison and Miller, Jason and Minx, Pat and Nusbaum, Chad and Russ, Carsten and Sykes, Sean M. and Tomlinson, Chad M. and Young, Sarah and Warren, Wesley C. and Badger, Jonathan and Crabtree, Jonathan and Markowitz, Victor M. and Orvis, Joshua and Cree, Andrew and Ferriera, Steve and Fulton, Lucinda L. and Fulton, Robert S. and Gillis, Marcus and Hemphill, Lisa D. and Joshi, Vandita and Kovar, Christie and Torralba, Manolito and Wetterstrand, Kris A. and Abouellleil, Amr and Wollam, Aye M. and Buhay, Christian J. and Ding, Yan and Dugan, Shannon and FitzGerald, Michael G. and Holder, Mike and Hostetler, Jessica and Clifton, Sandra W. and {Allen-Vercoe}, Emma and Earl, Ashlee M. and Farmer, Candace N. and Liolios, Konstantinos and Surette, Michael G. and Xu, Qiang and Pohl, Craig and {Wilczek-Boney}, Katarzyna and Zhu, Dianhui},
  year = {2010},
  month = may,
  volume = {328},
  pages = {994--999},
  issn = {1095-9203},
  doi = {10.1126/science.1183605},
  abstract = {The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97\%) were unique. In addition, this set of microbial genomes allows for approximately 40\% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.},
  journal = {Science (New York, N.Y.)},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {5981},
  pmcid = {PMC2940224},
  pmid = {20489017}
}

@article{huttenhowerStructureFunctionDiversity2012,
  title = {Structure, Function and Diversity of the Healthy Human Microbiome},
  author = {Huttenhower, Curtis and Gevers, Dirk and Knight, Rob and Abubucker, Sahar and Badger, Jonathan H. and Chinwalla, Asif T. and Creasy, Heather H. and Earl, Ashlee M. and FitzGerald, Michael G. and Fulton, Robert S. and Giglio, Michelle G. and {Hallsworth-Pepin}, Kymberlie and Lobos, Elizabeth A. and Madupu, Ramana and Magrini, Vincent and Martin, John C. and Mitreva, Makedonka and Muzny, Donna M. and Sodergren, Erica J. and Versalovic, James and Wollam, Aye M. and Worley, Kim C. and Wortman, Jennifer R. and Young, Sarah K. and Zeng, Qiandong and Aagaard, Kjersti M. and Abolude, Olukemi O. and {Allen-Vercoe}, Emma and Alm, Eric J. and Alvarado, Lucia and Andersen, Gary L. and Anderson, Scott and Appelbaum, Elizabeth and Arachchi, Harindra M. and Armitage, Gary and Arze, Cesar A. and Ayvaz, Tulin and Baker, Carl C. and Begg, Lisa and Belachew, Tsegahiwot and Bhonagiri, Veena and Bihan, Monika and Blaser, Martin J. and Bloom, Toby and Bonazzi, Vivien and Paul Brooks, J. and Buck, Gregory A. and Buhay, Christian J. and Busam, Dana A. and Campbell, Joseph L. and Canon, Shane R. and Cantarel, Brandi L. and Chain, Patrick S. G. and Chen, I-Min A. and Chen, Lei and Chhibba, Shaila and Chu, Ken and Ciulla, Dawn M. and Clemente, Jose C. and Clifton, Sandra W. and Conlan, Sean and Crabtree, Jonathan and Cutting, Mary A. and Davidovics, Noam J. and Davis, Catherine C. and DeSantis, Todd Z. and Deal, Carolyn and Delehaunty, Kimberley D. and Dewhirst, Floyd E. and Deych, Elena and Ding, Yan and Dooling, David J. and Dugan, Shannon P. and Michael Dunne, Wm and Scott Durkin, A. and Edgar, Robert C. and Erlich, Rachel L. and Farmer, Candace N. and Farrell, Ruth M. and Faust, Karoline and Feldgarden, Michael and Felix, Victor M. and Fisher, Sheila and Fodor, Anthony A. and Forney, Larry J. and Foster, Leslie and Di Francesco, Valentina and Friedman, Jonathan and Friedrich, Dennis C. and Fronick, Catrina C. and Fulton, Lucinda L. and Gao, Hongyu and Garcia, Nathalia and Giannoukos, Georgia and Giblin, Christina and Giovanni, Maria Y. and Goldberg, Jonathan M. and Goll, Johannes and Gonzalez, Antonio and Griggs, Allison and Gujja, Sharvari and Kinder Haake, Susan and Haas, Brian J. and Hamilton, Holli A. and Harris, Emily L. and Hepburn, Theresa A. and Herter, Brandi and Hoffmann, Diane E. and Holder, Michael E. and Howarth, Clinton and Huang, Katherine H. and Huse, Susan M. and Izard, Jacques and Jansson, Janet K. and Jiang, Huaiyang and Jordan, Catherine and Joshi, Vandita and Katancik, James A. and Keitel, Wendy A. and Kelley, Scott T. and Kells, Cristyn and King, Nicholas B. and Knights, Dan and Kong, Heidi H. and Koren, Omry and Koren, Sergey and Kota, Karthik C. and Kovar, Christie L. and Kyrpides, Nikos C. and La Rosa, Patricio S. and Lee, Sandra L. and Lemon, Katherine P. and Lennon, Niall and Lewis, Cecil M. and Lewis, Lora and Ley, Ruth E. and Li, Kelvin and Liolios, Konstantinos and Liu, Bo and Liu, Yue and Lo, Chien-Chi and Lozupone, Catherine A. and Dwayne Lunsford, R. and Madden, Tessa and Mahurkar, Anup A. and Mannon, Peter J. and Mardis, Elaine R. and Markowitz, Victor M. and Mavromatis, Konstantinos and McCorrison, Jamison M. and McDonald, Daniel and McEwen, Jean and McGuire, Amy L. and McInnes, Pamela and Mehta, Teena and Mihindukulasuriya, Kathie A. and Miller, Jason R. and Minx, Patrick J. and Newsham, Irene and Nusbaum, Chad and O'Laughlin, Michelle and Orvis, Joshua and Pagani, Ioanna and Palaniappan, Krishna and Patel, Shital M. and Pearson, Matthew and Peterson, Jane and Podar, Mircea and Pohl, Craig and Pollard, Katherine S. and Pop, Mihai and Priest, Margaret E. and Proctor, Lita M. and Qin, Xiang and Raes, Jeroen and Ravel, Jacques and Reid, Jeffrey G. and Rho, Mina and Rhodes, Rosamond and Riehle, Kevin P. and Rivera, Maria C. and {Rodriguez-Mueller}, Beltran and Rogers, Yu-Hui and Ross, Matthew C. and Russ, Carsten and Sanka, Ravi K. and Sankar, Pamela and Fah Sathirapongsasuti, J. and Schloss, Jeffery A. and Schloss, Patrick D. and Schmidt, Thomas M. and Scholz, Matthew and Schriml, Lynn and Schubert, Alyxandria M. and Segata, Nicola and Segre, Julia A. and Shannon, William D. and Sharp, Richard R. and Sharpton, Thomas J. and Shenoy, Narmada and Sheth, Nihar U. and Simone, Gina A. and Singh, Indresh and Smillie, Christopher S. and Sobel, Jack D. and Sommer, Daniel D. and Spicer, Paul and Sutton, Granger G. and Sykes, Sean M. and Tabbaa, Diana G. and Thiagarajan, Mathangi and Tomlinson, Chad M. and Torralba, Manolito and Treangen, Todd J. and Truty, Rebecca M. and Vishnivetskaya, Tatiana A. and Walker, Jason and Wang, Lu and Wang, Zhengyuan and Ward, Doyle V. and Warren, Wesley and Watson, Mark A. and Wellington, Christopher and Wetterstrand, Kris A. and White, James R. and {Wilczek-Boney}, Katarzyna and Wu, YuanQing and Wylie, Kristine M. and Wylie, Todd and Yandava, Chandri and Ye, Liang and Ye, Yuzhen and Yooseph, Shibu and Youmans, Bonnie P. and Zhang, Lan and Zhou, Yanjiao and Zhu, Yiming and Zoloth, Laurie and Zucker, Jeremy D. and Birren, Bruce W. and Gibbs, Richard A. and Highlander, Sarah K. and Meth{\'e}, Barbara A. and Nelson, Karen E. and Petrosino, Joseph F. and Weinstock, George M. and Wilson, Richard K. and White, Owen and {The Human Microbiome Project Consortium}},
  year = {2012},
  month = jun,
  volume = {486},
  pages = {207--214},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature11234},
  abstract = {Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81\textendash 99\% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.},
  copyright = {2012 The Author(s)},
  journal = {Nature},
  language = {en},
  number = {7402}
}

@article{hymanMicrobesHumanVaginal2005,
  title = {Microbes on the Human Vaginal Epithelium},
  author = {Hyman, Richard W. and Fukushima, Marilyn and Diamond, Lisa and Kumm, Jochen and Giudice, Linda C. and Davis, Ronald W.},
  year = {2005},
  month = may,
  volume = {102},
  pages = {7952--7957},
  issn = {0027-8424},
  doi = {10.1073/pnas.0503236102},
  abstract = {Using solely a gene-based procedure, PCR amplification of the 16S ribosomal RNA gene coupled with very deep sequencing of the amplified products, the microbes on 20 human vaginal epithelia of healthy women have been identified and quantitated. The Lactobacillus content on these 20 healthy vaginal epithelia was highly variable, ranging from 0\% to 100\%. For four subjects, Lactobacillus was (virtually) the only bacterium detected. However, that Lactobacillus was far from clonal and was a mixture of species and strains. Eight subjects presented complex mixtures of Lactobacillus and other microbes. The remaining eight subjects had no Lactobacillus. Instead, Bifidobacterium, Gardnerella, Prevotella, Pseudomonas, or Streptococcus predominated.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {技术进步,里程碑},
  language = {eng},
  number = {22},
  pmcid = {PMC1142396},
  pmid = {15911771}
}

@article{ilievInteractionsCommensalFungi2012,
  title = {Interactions between Commensal Fungi and the {{C}}-Type Lectin Receptor {{Dectin}}-1 Influence Colitis},
  author = {Iliev, Iliyan D. and Funari, Vincent A. and Taylor, Kent D. and Nguyen, Quoclinh and Reyes, Christopher N. and Strom, Samuel P. and Brown, Jordan and Becker, Courtney A. and Fleshner, Phillip R. and Dubinsky, Marla and Rotter, Jerome I. and Wang, Hanlin L. and McGovern, Dermot P. B. and Brown, Gordon D. and Underhill, David M.},
  year = {2012},
  month = jun,
  volume = {336},
  pages = {1314--1317},
  issn = {1095-9203},
  doi = {10.1126/science.1221789},
  abstract = {The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.},
  journal = {Science (New York, N.Y.)},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {6086},
  pmcid = {PMC3432565},
  pmid = {22674328}
}

@article{IntegrativeHumanMicrobiome2014,
  title = {The {{Integrative Human Microbiome Project}}: {{Dynamic Analysis}} of {{Microbiome}}-{{Host Omics Profiles}} during {{Periods}} of {{Human Health}} and {{Disease}}},
  shorttitle = {The {{Integrative Human Microbiome Project}}},
  year = {2014},
  month = sep,
  volume = {16},
  pages = {276--289},
  issn = {19313128},
  doi = {10.1016/j.chom.2014.08.014},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {3}
}

@article{ivanovInductionIntestinalTh172009,
  title = {Induction of {{Intestinal Th17 Cells}} by {{Segmented Filamentous Bacteria}}},
  author = {Ivanov, Ivaylo I. and Atarashi, Koji and Manel, Nicolas and Brodie, Eoin L. and Shima, Tatsuichiro and Karaoz, Ulas and Wei, Dongguang and Goldfarb, Katherine C. and Santee, Clark A. and Lynch, Susan V. and Tanoue, Takeshi and Imaoka, Akemi and Itoh, Kikuji and Takeda, Kiyoshi and Umesaki, Yoshinori and Honda, Kenya and Littman, Dan R.},
  year = {2009},
  month = oct,
  volume = {139},
  pages = {485--498},
  publisher = {{Elsevier}},
  issn = {0092-8674, 1097-4172},
  doi = {10.1016/j.cell.2009.09.033},
  abstract = {{$<$}h2{$>$}Summary{$<$}/h2{$><$}p{$>$}The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. How commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4\textsuperscript{+} T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation and antimicrobial defenses and resulted in enhanced resistance to the intestinal pathogen \emph{Citrobacter rodentium}. Thus, manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.{$<$}/p{$>$}},
  journal = {Cell},
  keywords = {粘膜免疫,里程碑},
  language = {English},
  number = {3},
  pmid = {19836068}
}

@article{ivanovSpecificMicrobiotaDirect2008,
  title = {Specific Microbiota Direct the Differentiation of {{IL}}-17-Producing {{T}}-Helper Cells in the Mucosa of the Small Intestine},
  author = {Ivanov, Ivaylo I. and Frutos, Rosa de Llanos and Manel, Nicolas and Yoshinaga, Keiji and Rifkin, Daniel B. and Sartor, R. Balfour and Finlay, B. Brett and Littman, Dan R.},
  year = {2008},
  month = oct,
  volume = {4},
  pages = {337--349},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2008.09.009},
  abstract = {The requirements for in vivo steady state differentiation of IL-17-producing T-helper (Th17) cells, which are potent inflammation effectors, remain obscure. We report that Th17 cell differentiation in the lamina propria (LP) of the small intestine requires specific commensal microbiota and is inhibited by treating mice with selective antibiotics. Mice from different sources had marked differences in their Th17 cell numbers and animals lacking Th17 cells acquired them after introduction of bacteria from Th17 cell-sufficient mice. Differentiation of Th17 cells correlated with the presence of cytophaga-flavobacter-bacteroidetes (CFB) bacteria in the intestine and was independent of toll-like receptor, IL-21 or IL-23 signaling, but required appropriate TGF-beta activation. Absence of Th17 cell-inducing bacteria was accompanied by increase in Foxp3+ regulatory T cells (Treg) in the LP. Our results suggest that composition of intestinal microbiota regulates the Th17:Treg balance in the LP and may thus influence intestinal immunity, tolerance, and susceptibility to inflammatory bowel diseases.},
  journal = {Cell Host \& Microbe},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {4},
  pmcid = {PMC2597589},
  pmid = {18854238}
}

@article{jakobssonDecreasedGutMicrobiota2014,
  title = {Decreased Gut Microbiota Diversity, Delayed {{Bacteroidetes}} Colonisation and Reduced {{Th1}} Responses in Infants Delivered by Caesarean Section},
  author = {Jakobsson, Hedvig E. and Abrahamsson, Thomas R. and Jenmalm, Maria C. and Harris, Keith and Quince, Christopher and Jernberg, Cecilia and Bj{\"o}rkst{\'e}n, Bengt and Engstrand, Lars and Andersson, Anders F.},
  year = {2014},
  month = apr,
  volume = {63},
  pages = {559--566},
  issn = {1468-3288},
  doi = {10.1136/gutjnl-2012-303249},
  abstract = {OBJECTIVE: The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. DESIGN: The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. RESULTS: Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. CONCLUSIONS: CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.},
  journal = {Gut},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {4},
  pmid = {23926244}
}

@article{jiangCommensalFungiRecapitulate2017,
  title = {Commensal {{Fungi Recapitulate}} the {{Protective Benefits}} of {{Intestinal Bacteria}}},
  author = {Jiang, Tony T. and Shao, Tzu-Yu and Ang, W. X. Gladys and Kinder, Jeremy M. and Turner, Lucien H. and Pham, Giang and Whitt, Jordan and Alenghat, Theresa and Way, Sing Sing},
  year = {2017},
  month = dec,
  volume = {22},
  pages = {809-816.e4},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2017.10.013},
  abstract = {Commensal intestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensal microbes remain poorly defined. Here, we show that commensal fungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenza A virus infection occurring upon commensal bacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae. The protective benefits of commensal fungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensal bacteria. Thus, commensal enteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria.},
  journal = {Cell Host \& Microbe},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {6},
  pmcid = {PMC5730478},
  pmid = {29174402}
}

@article{kaoEffectOralCapsule2017,
  title = {Effect of {{Oral Capsule}}- vs {{Colonoscopy}}-{{Delivered Fecal Microbiota Transplantation}} on {{Recurrent Clostridium}} Difficile {{Infection}}: {{A Randomized Clinical Trial}}},
  shorttitle = {Effect of {{Oral Capsule}}- vs {{Colonoscopy}}-{{Delivered Fecal Microbiota Transplantation}} on {{Recurrent Clostridium}} Difficile {{Infection}}},
  author = {Kao, Dina and Roach, Brandi and Silva, Marisela and Beck, Paul and Rioux, Kevin and Kaplan, Gilaad G. and Chang, Hsiu-Ju and Coward, Stephanie and Goodman, Karen J. and Xu, Huiping and Madsen, Karen and Mason, Andrew and Wong, Gane Ka-Shu and Jovel, Juan and Patterson, Jordan and Louie, Thomas},
  year = {2017},
  month = nov,
  volume = {318},
  pages = {1985--1993},
  issn = {1538-3598},
  doi = {10.1001/jama.2017.17077},
  abstract = {Importance: Fecal microbiota transplantation (FMT) is effective in preventing recurrent Clostridium difficile infection (RCDI). However, it is not known whether clinical efficacy differs by route of delivery. Objective: To determine whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy. Design, Setting, and Participants: Noninferiority, unblinded, randomized trial conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients with RCDI were enrolled between October 2014 and September 2016, with follow-up to December 2016. The noninferiority margin was 15\%. Interventions: Participants were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio. Main Outcomes and Measures: The primary outcome was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor adverse events, (2) changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst). Results: Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women [68\%]), 105 (91\%) completed the trial, with 57 patients randomized to the capsule group and 59 to the colonoscopy group. In per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2\% in both the capsule group (51/53) and the colonoscopy group (50/52) (difference, 0\%; 1-sided 95\% CI, -6.1\% to infinity; P\,{$<$}\,.001), meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of minor adverse events were 5.4\% for the capsule group vs 12.5\% for the colonoscopy group. There was no significant between-group difference in improvement in quality of life. A significantly greater proportion of participants receiving capsules rated their experience as "not at all unpleasant" (66\% vs 44\%; difference, 22\% [95\% CI, 3\%-40\%]; P\,=\,.01). Conclusions and Relevance: Among adults with RCDI, FMT via oral capsules was not inferior to delivery by colonoscopy for preventing recurrent infection over 12 weeks. Treatment with oral capsules may be an effective approach to treating RCDI. Trial Registration: clinicaltrials.gov Identifier: NCT02254811.},
  journal = {JAMA},
  keywords = {Administration; Oral,Adult,Aged,Aged; 80 and over,Capsules,Clostridium Infections,Colonoscopy,Fecal Microbiota Transplantation,Feces,Female,Humans,Male,Middle Aged,Patient Satisfaction,Quality of Life,Secondary Prevention,Young Adult,粪菌移植,里程碑},
  language = {eng},
  number = {20},
  pmcid = {PMC5820695},
  pmid = {29183074}
}

@article{karlssonGutMetagenomeEuropean2013,
  title = {Gut Metagenome in {{European}} Women with Normal, Impaired and Diabetic Glucose Control},
  author = {Karlsson, Fredrik H. and Tremaroli, Valentina and Nookaew, Intawat and Bergstr{\"o}m, G{\"o}ran and Behre, Carl Johan and Fagerberg, Bj{\"o}rn and Nielsen, Jens and B{\"a}ckhed, Fredrik},
  year = {2013},
  month = jun,
  volume = {498},
  pages = {99--103},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature12198},
  abstract = {The faecal metagenome of a cohort of 145 European women with normal, impaired or diabetic glucose control was characterized and discriminant metagenomic markers for type 2 diabetes were identified; the discriminant markers differed from those of a recent Chinese cohort, suggesting that metagenomic predictive tools may need to be specific for age and geographic location.},
  copyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7452}
}

@article{karlssonSymptomaticAtherosclerosisAssociated2012,
  title = {Symptomatic Atherosclerosis Is Associated with an Altered Gut Metagenome},
  author = {Karlsson, Fredrik H. and F{\aa}k, Frida and Nookaew, Intawat and Tremaroli, Valentina and Fagerberg, Bj{\"o}rn and Petranovic, Dina and B{\"a}ckhed, Fredrik and Nielsen, Jens},
  year = {2012},
  month = dec,
  volume = {3},
  pages = {1245},
  publisher = {{Nature Publishing Group}},
  issn = {2041-1723},
  doi = {10.1038/ncomms2266},
  abstract = {Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of {$\beta$}-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.},
  copyright = {2012 The Author(s)},
  journal = {Nature Communications},
  language = {en},
  number = {1}
}

@article{klattVaginalBacteriaModify2017,
  title = {Vaginal Bacteria Modify {{HIV}} Tenofovir Microbicide Efficacy in {{African}} Women},
  author = {Klatt, Nichole R. and Cheu, Ryan and Birse, Kenzie and Zevin, Alexander S. and Perner, Michelle and {No{\"e}l-Romas}, Laura and Grobler, Anneke and Westmacott, Garrett and Xie, Irene Y. and Butler, Jennifer and Mansoor, Leila and McKinnon, Lyle R. and Passmore, Jo-Ann S. and Abdool Karim, Quarraisha and Abdool Karim, Salim S. and Burgener, Adam D.},
  year = {2017},
  month = feb,
  volume = {356},
  pages = {938--945},
  issn = {1095-9203},
  doi = {10.1126/science.aai9383},
  abstract = {Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial. Two major vaginal bacterial community types-one dominated by Lactobacillus (59.2\%) and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (40.8\%)-were identified in 688 women profiled. Tenofovir reduced HIV incidence by 61\% (P = 0.013) in Lactobacillus-dominant women but only 18\% (P = 0.644) in women with non-Lactobacillus bacteria, a threefold difference in efficacy. Detectible mucosal tenofovir was lower in non-Lactobacillus women, negatively correlating with G. vaginalis and other anaerobic bacteria, which depleted tenofovir by metabolism more rapidly than target cells convert to pharmacologically active drug. This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism.},
  journal = {Science (New York, N.Y.)},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {6341},
  pmid = {28572388}
}

@article{knightsRethinkingEnterotypes2014,
  title = {Rethinking ``{{Enterotypes}}''},
  author = {Knights, Dan and Ward, Tonya L. and McKinlay, Christopher E. and Miller, Hannah and Gonzalez, Antonio and McDonald, Daniel and Knight, Rob},
  year = {2014},
  month = oct,
  volume = {16},
  pages = {433--437},
  issn = {19313128},
  doi = {10.1016/j.chom.2014.09.013},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {4}
}

@article{koenigSuccessionMicrobialConsortia2011,
  title = {Succession of Microbial Consortia in the Developing Infant Gut Microbiome},
  author = {Koenig, Jeremy E. and Spor, Aym{\'e} and Scalfone, Nicholas and Fricker, Ashwana D. and Stombaugh, Jesse and Knight, Rob and Angenent, Largus T. and Ley, Ruth E.},
  year = {2011},
  month = mar,
  volume = {108 Suppl 1},
  pages = {4578--4585},
  issn = {1091-6490},
  doi = {10.1073/pnas.1000081107},
  abstract = {The colonization process of the infant gut microbiome has been called chaotic, but this view could reflect insufficient documentation of the factors affecting the microbiome. We performed a 2.5-y case study of the assembly of the human infant gut microbiome, to relate life events to microbiome composition and function. Sixty fecal samples were collected from a healthy infant along with a diary of diet and health status. Analysis of {$>$}300,000 16S rRNA genes indicated that the phylogenetic diversity of the microbiome increased gradually over time and that changes in community composition conformed to a smooth temporal gradient. In contrast, major taxonomic groups showed abrupt shifts in abundance corresponding to changes in diet or health. Community assembly was nonrandom: we observed discrete steps of bacterial succession punctuated by life events. Furthermore, analysis of {$\approx$} 500,000 DNA metagenomic reads from 12 fecal samples revealed that the earliest microbiome was enriched in genes facilitating lactate utilization, and that functional genes involved in plant polysaccharide metabolism were present before the introduction of solid food, priming the infant gut for an adult diet. However, ingestion of table foods caused a sustained increase in the abundance of Bacteroidetes, elevated fecal short chain fatty acid levels, enrichment of genes associated with carbohydrate utilization, vitamin biosynthesis, and xenobiotic degradation, and a more stable community composition, all of which are characteristic of the adult microbiome. This study revealed that seemingly chaotic shifts in the microbiome are associated with life events; however, additional experiments ought to be conducted to assess how different infants respond to similar life events.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {菌群发育,里程碑},
  language = {eng},
  pmcid = {PMC3063592},
  pmid = {20668239}
}

@article{koethGButyrobetaineProatherogenicIntermediate2014,
  title = {{$\gamma$}-{{Butyrobetaine Is}} a {{Proatherogenic Intermediate}} in {{Gut Microbial Metabolism}} of {{L}}-{{Carnitine}} to {{TMAO}}},
  author = {Koeth, Robert A. and Levison, Bruce S. and Culley, Miranda K. and Buffa, Jennifer A. and Wang, Zeneng and Gregory, Jill C. and Org, Elin and Wu, Yuping and Li, Lin and Smith, Jonathan D. and Tang, W. H. Wilson and DiDonato, Joseph A. and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2014},
  month = nov,
  volume = {20},
  pages = {799--812},
  publisher = {{Elsevier}},
  issn = {1550-4131},
  doi = {10.1016/j.cmet.2014.10.006},
  abstract = {{$<$}h2{$>$}Summary{$<$}/h2{$><$}p{$>$}\emph{L}-carnitine, a nutrient in red meat, was recently reported to accelerate atherosclerosis via a metaorganismal pathway involving gut microbial trimethylamine (TMA) formation and host hepatic conversion into trimethylamine-\emph{N}-oxide (TMAO). Herein, we show that following \emph{L}-carnitine ingestion, {$\gamma$}-butyrobetaine ({$\gamma$}BB) is produced as an intermediary metabolite by gut microbes at a site anatomically proximal to and at a rate {$\sim$}1,000-fold higher than the formation of TMA. Moreover, we show that {$\gamma$}BB is the major gut microbial metabolite formed from dietary \emph{L}-carnitine in mice, is converted into TMA and TMAO in a gut microbiota-dependent manner (like dietary \emph{L}-carnitine), and accelerates atherosclerosis. Gut microbial composition and functional metabolic studies reveal that distinct taxa are associated with the production of {$\gamma$}BB or TMA/TMAO from dietary \emph{L}-carnitine. Moreover, despite their close structural similarity, chronic dietary exposure to \emph{L}-carnitine or {$\gamma$}BB promotes development of functionally distinct microbial communities optimized for the metabolism of \emph{L}-carnitine or {$\gamma$}BB, respectively.{$<$}/p{$>$}},
  journal = {Cell Metabolism},
  language = {English},
  number = {5},
  pmid = {25440057}
}

@article{koethIntestinalMicrobiotaMetabolism2013,
  title = {Intestinal Microbiota Metabolism of {{L}}-Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis},
  author = {Koeth, Robert A. and Wang, Zeneng and Levison, Bruce S. and Buffa, Jennifer A. and Org, Elin and Sheehy, Brendan T. and Britt, Earl B. and Fu, Xiaoming and Wu, Yuping and Li, Lin and Smith, Jonathan D. and DiDonato, Joseph A. and Chen, Jun and Li, Hongzhe and Wu, Gary D. and Lewis, James D. and Warrier, Manya and Brown, J. Mark and Krauss, Ronald M. and Tang, W. H. Wilson and Bushman, Frederic D. and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2013},
  month = may,
  volume = {19},
  pages = {576--585},
  issn = {1078-8956},
  doi = {10.1038/nm.3145},
  abstract = {Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.},
  journal = {Nature medicine},
  keywords = {喂养菌群,里程碑},
  number = {5},
  pmcid = {PMC3650111},
  pmid = {23563705}
}

@article{koppelChemicalTransformationXenobiotics2017,
  title = {Chemical Transformation of Xenobiotics by the Human Gut Microbiota},
  author = {Koppel, Nitzan and Maini Rekdal, Vayu and Balskus, Emily P.},
  year = {2017},
  month = jun,
  volume = {356},
  issn = {1095-9203},
  doi = {10.1126/science.aag2770},
  abstract = {The human gut microbiota makes key contributions to the metabolism of ingested compounds (xenobiotics), transforming hundreds of dietary components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes within the body. The chemistry of gut microbial xenobiotic metabolism is often distinct from that of host enzymes. Despite their important consequences for human biology, the gut microbes, genes, and enzymes involved in xenobiotic metabolism are poorly understood. Linking these microbial transformations to enzymes and elucidating their biological effects is undoubtedly challenging. However, recent studies demonstrate that integrating traditional and emerging technologies can enable progress toward this goal. Ultimately, a molecular understanding of gut microbial xenobiotic metabolism will guide personalized medicine and nutrition, inform toxicology risk assessment, and improve drug discovery and development.},
  journal = {Science (New York, N.Y.)},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {6344},
  pmcid = {PMC5534341},
  pmid = {28642381}
}

@article{korenHumanOralGut2011,
  title = {Human Oral, Gut, and Plaque Microbiota in Patients with Atherosclerosis},
  author = {Koren, Omry and Spor, Aym{\'e} and Felin, Jenny and F{\aa}k, Frida and Stombaugh, Jesse and Tremaroli, Valentina and Behre, Carl Johan and Knight, Rob and Fagerberg, Bj{\"o}rn and Ley, Ruth E. and B{\"a}ckhed, Fredrik},
  year = {2011},
  month = mar,
  volume = {108},
  pages = {4592--4598},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.1011383107},
  abstract = {Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis.},
  chapter = {Colloquium Paper},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {Supplement 1},
  pmid = {20937873}
}

@article{koskinenFirstInsightsDiverse2017,
  title = {First {{Insights}} into the {{Diverse Human Archaeome}}: {{Specific Detection}} of {{Archaea}} in the {{Gastrointestinal Tract}}, {{Lung}}, and {{Nose}} and on {{Skin}}},
  shorttitle = {First {{Insights}} into the {{Diverse Human Archaeome}}},
  author = {Koskinen, Kaisa and Pausan, Manuela R. and Perras, Alexandra K. and Beck, Michael and Bang, Corinna and Mora, Maximilian and Schilhabel, Anke and Schmitz, Ruth and {Moissl-Eichinger}, Christine},
  year = {2017},
  month = nov,
  volume = {8},
  issn = {2150-7511},
  doi = {10.1128/mBio.00824-17},
  abstract = {Human-associated archaea remain understudied in the field of microbiome research, although in particular methanogenic archaea were found to be regular commensals of the human gut, where they represent keystone species in metabolic processes. Knowledge on the abundance and diversity of human-associated archaea is extremely limited, and little is known about their function(s), their overall role in human health, or their association with parts of the human body other than the gastrointestinal tract and oral cavity. Currently, methodological issues impede the full assessment of the human archaeome, as bacteria-targeting protocols are unsuitable for characterization of the full spectrum of Archaea The goal of this study was to establish conservative protocols based on specifically archaea-targeting, PCR-based methods to retrieve first insights into the archaeomes of the human gastrointestinal tract, lung, nose, and skin. Detection of Archaea was highly dependent on primer selection and the sequence processing pipeline used. Our results enabled us to retrieve a novel picture of the human archaeome, as we found for the first time Methanobacterium and Woesearchaeota (DPANN superphylum) to be associated with the human gastrointestinal tract and the human lung, respectively. Similar to bacteria, human-associated archaeal communities were found to group biogeographically, forming (i) the thaumarchaeal skin landscape, (ii) the (methano)euryarchaeal gastrointestinal tract, (iii) a mixed skin-gastrointestinal tract landscape for the nose, and (iv) a woesearchaeal lung landscape. On the basis of the protocols we used, we were able to detect unexpectedly high diversity of archaea associated with different body parts.IMPORTANCE In summary, our study highlights the importance of the primers and data processing pipeline used to study the human archaeome. We were able to establish protocols that revealed the presence of previously undetected Archaea in all of the tissue samples investigated and to detect biogeographic patterns of the human archaeome in the gastrointestinal tract and on the skin and for the first time in the respiratory tract, i.e., the nose and lungs. Our results are a solid basis for further investigation of the human archaeome and, in the long term, discovery of the potential role of archaea in human health and disease.},
  journal = {mBio},
  keywords = {古菌,里程碑},
  language = {eng},
  number = {6},
  pmcid = {PMC5686531},
  pmid = {29138298}
}

@article{kosticDynamicsHumanInfant2015,
  title = {The {{Dynamics}} of the {{Human Infant Gut Microbiome}} in {{Development}} and in {{Progression}} toward {{Type}} 1 {{Diabetes}}},
  author = {Kostic, Aleksandar D. and Gevers, Dirk and Siljander, Heli and Vatanen, Tommi and Hy{\"o}tyl{\"a}inen, Tuulia and H{\"a}m{\"a}l{\"a}inen, Anu-Maaria and Peet, Aleksandr and Tillmann, Vallo and P{\"o}h{\"o}, P{\"a}ivi and Mattila, Ismo and L{\"a}hdesm{\"a}ki, Harri and Franzosa, Eric A. and Vaarala, Outi and {de Goffau}, Marcus and Harmsen, Hermie and Ilonen, Jorma and Virtanen, Suvi M. and Clish, Clary B. and Ore{\v s}i{\v c}, Matej and Huttenhower, Curtis and Knip, Mikael and Xavier, Ramnik J.},
  year = {2015},
  month = feb,
  volume = {17},
  pages = {260--273},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.01.001},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {2}
}

@article{kosticGenomicAnalysisIdentifies2012,
  title = {Genomic Analysis Identifies Association of {{Fusobacterium}} with Colorectal Carcinoma},
  author = {Kostic, Aleksandar D. and Gevers, Dirk and Pedamallu, Chandra Sekhar and Michaud, Monia and Duke, Fujiko and Earl, Ashlee M. and Ojesina, Akinyemi I. and Jung, Joonil and Bass, Adam J. and Tabernero, Josep and Baselga, Jos{\'e} and Liu, Chen and Shivdasani, Ramesh A. and Ogino, Shuji and Birren, Bruce W. and Huttenhower, Curtis and Garrett, Wendy S. and Meyerson, Matthew},
  year = {2012},
  month = jan,
  volume = {22},
  pages = {292--298},
  publisher = {{Cold Spring Harbor Lab}},
  issn = {1088-9051, 1549-5469},
  doi = {10.1101/gr.126573.111},
  abstract = {The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation.},
  journal = {Genome Research},
  language = {en},
  number = {2},
  pmid = {22009990}
}

@article{lagierCulturingHumanMicrobiota2018,
  title = {Culturing the Human Microbiota and Culturomics},
  author = {Lagier, Jean-Christophe and Dubourg, Gr{\'e}gory and Million, Matthieu and Cadoret, Fr{\'e}d{\'e}ric and Bilen, Melhem and Fenollar, Florence and Levasseur, Anthony and Rolain, Jean-Marc and Fournier, Pierre-Edouard and Raoult, Didier},
  year = {2018},
  month = sep,
  volume = {16},
  pages = {540--550},
  publisher = {{Nature Publishing Group}},
  issn = {1740-1534},
  doi = {10.1038/s41579-018-0041-0},
  abstract = {Culturomics was developed to culture and identify unknown bacteria that inhabit the human gut. In this Review, Raoult and colleagues discuss the development of culturomics and how it has extended our understanding of bacterial diversity, and highlight the potential implications for human health.},
  copyright = {2018 Macmillan Publishers Ltd., part of Springer Nature},
  journal = {Nature Reviews Microbiology},
  keywords = {培养组学,里程碑},
  language = {en},
  number = {9}
}

@article{lagierMicrobialCulturomicsParadigm2012,
  title = {Microbial Culturomics: Paradigm Shift in the Human Gut Microbiome Study},
  shorttitle = {Microbial Culturomics},
  author = {Lagier, J.-C. and Armougom, F. and Million, M. and Hugon, P. and Pagnier, I. and Robert, C. and Bittar, F. and Fournous, G. and Gimenez, G. and Maraninchi, M. and Trape, J.-F. and Koonin, E. V. and La Scola, B. and Raoult, D.},
  year = {2012},
  month = dec,
  volume = {18},
  pages = {1185--1193},
  issn = {1469-0691},
  doi = {10.1111/1469-0691.12023},
  abstract = {Comprehensive determination of the microbial composition of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic analysis of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analysed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes, five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future molecular studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic analysis of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches.},
  journal = {Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases},
  keywords = {Biodiversity,Feces,Gastrointestinal Tract,Humans,Male,Mass Spectrometry,Metagenome,Metagenomics,Microbiological Techniques,Molecular Sequence Data,Sequence Analysis; DNA,培养组学,里程碑},
  language = {eng},
  number = {12},
  pmid = {23033984}
}

@article{lahtiTippingElementsHuman2014,
  title = {Tipping Elements in the Human Intestinal Ecosystem},
  author = {Lahti, Leo and Saloj{\"a}rvi, Jarkko and Salonen, Anne and Scheffer, Marten and {de Vos}, Willem M.},
  year = {2014},
  month = jul,
  volume = {5},
  pages = {1--10},
  publisher = {{Nature Publishing Group}},
  issn = {2041-1723},
  doi = {10.1038/ncomms5344},
  abstract = {Intestinal microbes can have important effects on our health. Here, the authors analyse the gut microbiota composition in 1,000 western adults and find that certain bacteria are either abundant or nearly absent, and that these alternative states are associated with ageing and overweight.},
  copyright = {2014 The Author(s)},
  journal = {Nature Communications},
  keywords = {菌群稳定性,里程碑},
  language = {en},
  number = {1}
}

@article{larsenGutMicrobiotaHuman2010,
  title = {Gut {{Microbiota}} in {{Human Adults}} with {{Type}} 2 {{Diabetes Differs}} from {{Non}}-{{Diabetic Adults}}},
  author = {Larsen, Nadja and Vogensen, Finn K. and van den Berg, Frans W. J. and Nielsen, Dennis Sandris and Andreasen, Anne Sofie and Pedersen, Bente K. and {Al-Soud}, Waleed Abu and S{\o}rensen, S{\o}ren J. and Hansen, Lars H. and Jakobsen, Mogens},
  year = {2010},
  month = feb,
  volume = {5},
  pages = {e9085},
  publisher = {{Public Library of Science}},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0009085},
  abstract = {Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control. Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03). Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04) but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02) and positively correlated with plasma glucose (P = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.},
  journal = {PLOS ONE},
  language = {en},
  number = {2}
}

@article{lechatelierRichnessHumanGut2013b,
  title = {Richness of Human Gut Microbiome Correlates with Metabolic Markers},
  author = {Le Chatelier, Emmanuelle and Nielsen, Trine and Qin, Junjie and Prifti, Edi and Hildebrand, Falk and Falony, Gwen and Almeida, Mathieu and Arumugam, Manimozhiyan and Batto, Jean-Michel and Kennedy, Sean and Leonard, Pierre and Li, Junhua and Burgdorf, Kristoffer and Grarup, Niels and J{\o}rgensen, Torben and Brandslund, Ivan and Nielsen, Henrik Bj{\o}rn and Juncker, Agnieszka S. and Bertalan, Marcelo and Levenez, Florence and Pons, Nicolas and Rasmussen, Simon and Sunagawa, Shinichi and Tap, Julien and Tims, Sebastian and Zoetendal, Erwin G. and Brunak, S{\o}ren and Cl{\'e}ment, Karine and Dor{\'e}, Jo{\"e}l and Kleerebezem, Michiel and Kristiansen, Karsten and Renault, Pierre and {Sicheritz-Ponten}, Thomas and {de Vos}, Willem M. and Zucker, Jean-Daniel and Raes, Jeroen and Hansen, Torben and Bork, Peer and Wang, Jun and Ehrlich, S. Dusko and Pedersen, Oluf},
  year = {2013},
  month = aug,
  volume = {500},
  pages = {541--546},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature12506},
  abstract = {We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23\% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.},
  copyright = {2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7464}
}

@article{leppMethanogenicArchaeaHuman2004,
  title = {Methanogenic {{Archaea}} and Human Periodontal Disease},
  author = {Lepp, Paul W. and Brinig, Mary M. and Ouverney, Cleber C. and Palm, Katherine and Armitage, Gary C. and Relman, David A.},
  year = {2004},
  month = apr,
  volume = {101},
  pages = {6176--6181},
  issn = {0027-8424},
  doi = {10.1073/pnas.0308766101},
  abstract = {Archaea have been isolated from the human colon, vagina, and oral cavity, but have not been established as causes of human disease. In this study, we reveal a relationship between the severity of periodontal disease and the relative abundance of archaeal small subunit ribosomal RNA genes (SSU rDNA) in the subgingival crevice by using quantitative PCR. Furthermore, the relative abundance of archaeal small subunit rDNA decreased at treated sites in association with clinical improvement. Archaea were harbored by 36\% of periodontitis patients and were restricted to subgingival sites with periodontal disease. The presence of archaeal cells at these sites was confirmed by fluorescent in situ hybridization. The archaeal community at diseased sites was dominated by a Methanobrevibacter oralis-like phylotype and a distinct Methanobrevibacter subpopulation related to archaea that inhabit the gut of numerous animals. We hypothesize that methanogens participate in syntrophic relationships in the subgingival crevice that promote colonization by secondary fermenters during periodontitis. Because they are potential alternative syntrophic partners, our finding of larger Treponema populations sites without archaea provides further support for this hypothesis.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {古菌,里程碑},
  language = {eng},
  number = {16},
  pmcid = {PMC395942},
  pmid = {15067114}
}

@article{lewisInflammationAntibioticsDiet2015,
  title = {Inflammation, {{Antibiotics}}, and {{Diet}} as {{Environmental Stressors}} of the {{Gut Microbiome}} in {{Pediatric Crohn}}'s {{Disease}}},
  author = {Lewis, James D. and Chen, Eric Z. and Baldassano, Robert N. and Otley, Anthony R. and Griffiths, Anne M. and Lee, Dale and Bittinger, Kyle and Bailey, Aubrey and Friedman, Elliot S. and Hoffmann, Christian and Albenberg, Lindsey and Sinha, Rohini and Compher, Charlene and Gilroy, Erin and Nessel, Lisa and Grant, Amy and Chehoud, Christel and Li, Hongzhe and Wu, Gary D. and Bushman, Frederic D.},
  year = {2015},
  month = oct,
  volume = {18},
  pages = {489--500},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.09.008},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {4}
}

@article{leyHumanGutMicrobes2006,
  title = {Human Gut Microbes Associated with Obesity},
  author = {Ley, Ruth E. and Turnbaugh, Peter J. and Klein, Samuel and Gordon, Jeffrey I.},
  year = {2006},
  month = dec,
  volume = {444},
  pages = {1022--1023},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/4441022a},
  abstract = {Our gut microbes do us a service by performing metabolic chores that we have not evolved to do for ourselves. In a sense their genes are part of the 'metagenome' that is Homo sapiens. That is illustrated by two related papers in this issue that present evidence for a microbial component to obesity. A study of the abundance of the two dominant groups of bacteria in the gut of obese individuals shows that increased numbers of Bacteroidetes bacteria correlate with weight loss. And a study of genetically obese mice reveals that their gut microbial community has a greater capacity for harvesting energy than that of lean littermates: the trait is transmissible by transplanting the community into germ-free mice. This work suggests that the gut microbiome associated with obesity might be a biomarker and possibly a therapeutic target.},
  copyright = {2006 Nature Publishing Group},
  journal = {Nature},
  language = {en},
  number = {7122}
}

@article{leyObesityAltersGut2005,
  title = {Obesity Alters Gut Microbial Ecology},
  author = {Ley, Ruth E. and B{\"a}ckhed, Fredrik and Turnbaugh, Peter and Lozupone, Catherine A. and Knight, Robin D. and Gordon, Jeffrey I.},
  year = {2005},
  month = aug,
  volume = {102},
  pages = {11070--11075},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.0504978102},
  abstract = {We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50\% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.},
  chapter = {Biological Sciences},
  copyright = {Copyright \textcopyright{} 2005, The National Academy of Sciences.                       Freely available online through the PNAS open access option.},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {31},
  pmid = {16033867}
}

@article{liangBidirectionalInteractionsIndomethacin2015,
  title = {Bidirectional Interactions between Indomethacin and the Murine Intestinal Microbiota},
  author = {Liang, Xue and Bittinger, Kyle and Li, Xuanwen and Abernethy, Darrell R. and Bushman, Frederic D. and FitzGerald, Garret A.},
  year = {2015},
  month = dec,
  volume = {4},
  pages = {e08973},
  issn = {2050-084X},
  doi = {10.7554/eLife.08973},
  abstract = {The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial {$\beta$}-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin - thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses.},
  journal = {eLife},
  keywords = {药物代谢,里程碑},
  language = {eng},
  pmcid = {PMC4755745},
  pmid = {26701907}
}

@article{liDurableCoexistenceDonor2016,
  title = {Durable Coexistence of Donor and Recipient Strains after Fecal Microbiota Transplantation},
  author = {Li, S. S. and Zhu, A. and Benes, V. and Costea, P. I. and Hercog, R. and Hildebrand, F. and {Huerta-Cepas}, J. and Nieuwdorp, M. and Salojarvi, J. and Voigt, A. Y. and Zeller, G. and Sunagawa, S. and {de Vos}, W. M. and Bork, P.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {586--589},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad8852},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{limEarlyLifeDynamics2015,
  title = {Early Life Dynamics of the Human Gut Virome and Bacterial Microbiome in Infants},
  author = {Lim, Efrem S. and Zhou, Yanjiao and Zhao, Guoyan and Bauer, Irma K. and Droit, Lindsay and Ndao, I. Malick and Warner, Barbara B. and Tarr, Phillip I. and Wang, David and Holtz, Lori R.},
  year = {2015},
  month = oct,
  volume = {21},
  pages = {1228--1234},
  issn = {1546-170X},
  doi = {10.1038/nm.3950},
  abstract = {The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age.},
  journal = {Nature Medicine},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {10},
  pmcid = {PMC4710368},
  pmid = {26366711}
}

@article{lindenbaumInactivationDigoxinGut1981,
  title = {Inactivation of Digoxin by the Gut Flora: Reversal by Antibiotic Therapy},
  shorttitle = {Inactivation of Digoxin by the Gut Flora},
  author = {Lindenbaum, J. and Rund, D. G. and Butler, V. P. and {Tse-Eng}, D. and Saha, J. R.},
  year = {1981},
  month = oct,
  volume = {305},
  pages = {789--794},
  issn = {0028-4793},
  doi = {10.1056/NEJM198110013051403},
  abstract = {In approximately 10 per cent of patients given digoxin, substantial conversion of the drug to cardioinactive, reduced metabolites (digoxin reduction products, or DRPs) occurs. The site and clinical importance of this conversion is unknown. In four normal volunteers taking digoxin daily for four weeks, urinary excretion of DRPs was greatest after a poorly absorbed tablet was ingested, and least after intravenous administration, Stool cultures from subjects known to make DRPs in vivo ("excretors") converted digoxin to DRPs; cultures from nonexcretors did not. Three excretors were given tablets for 22 to 29 days. A five-day course of erythromycin or tetracycline, administered after a base-line period of 10 to 17 days, markedly reduced or eliminated DRP excretion in urine and stool. Serum digoxin concentrations rose as much as twofold after antibiotics were given. We conclude that in some persons digoxin is inactivated by gastrointestinal bacteria. Changes in the enteric flora may markedly alter the state of digitalization.},
  journal = {The New England Journal of Medicine},
  keywords = {Anti-Bacterial Agents,Bacteria,Biological Availability,Digestive System,Digoxin,Drug Interactions,Erythromycin,Feces,Female,Humans,Male,Tetracycline,药物转化,里程碑},
  language = {eng},
  number = {14},
  pmid = {7266632}
}

@article{lloyd-priceStrainsFunctionsDynamics2017,
  title = {Strains, Functions and Dynamics in the Expanded {{Human Microbiome Project}}},
  author = {{Lloyd-Price}, Jason and Mahurkar, Anup and Rahnavard, Gholamali and Crabtree, Jonathan and Orvis, Joshua and Hall, A. Brantley and Brady, Arthur and Creasy, Heather H. and McCracken, Carrie and Giglio, Michelle G. and McDonald, Daniel and Franzosa, Eric A. and Knight, Rob and White, Owen and Huttenhower, Curtis},
  year = {2017},
  month = oct,
  volume = {550},
  pages = {61--66},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature23889},
  abstract = {Updates from the Human Microbiome Project analyse the largest known body-wide metagenomic profile of human microbiome personalization.},
  copyright = {2017 The Author(s)},
  journal = {Nature},
  keywords = {菌群稳定性,里程碑},
  language = {en},
  number = {7674}
}

@article{macphersonPrimitiveCellindependentMechanism2000,
  title = {A Primitive {{T}} Cell-Independent Mechanism of Intestinal Mucosal {{IgA}} Responses to Commensal Bacteria},
  author = {Macpherson, A. J. and Gatto, D. and Sainsbury, E. and Harriman, G. R. and Hengartner, H. and Zinkernagel, R. M.},
  year = {2000},
  month = jun,
  volume = {288},
  pages = {2222--2226},
  issn = {0036-8075},
  doi = {10.1126/science.288.5474.2222},
  abstract = {The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood. The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply "natural antibody" but was specifically induced and responded to antigenic changes within an established gut flora. In contrast to IgA responses against exotoxins, a significant proportion of this specific anti-commensal IgA induction was through a pathway that was independent of T cell help and of follicular lymphoid tissue organization, which may reflect an evolutionarily primitive form of specific immune defense.},
  journal = {Science (New York, N.Y.)},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {5474},
  pmid = {10864873}
}

@article{maldonado-gomezStableEngraftmentBifidobacterium2016,
  title = {Stable {{Engraftment}} of {{Bifidobacterium}} Longum {{AH1206}} in the {{Human Gut Depends}} on {{Individualized Features}} of the {{Resident Microbiome}}},
  author = {{Maldonado-G{\'o}mez}, Mar{\'i}a X. and Mart{\'i}nez, In{\'e}s and Bottacini, Francesca and O'Callaghan, Amy and Ventura, Marco and {van Sinderen}, Douwe and Hillmann, Benjamin and Vangay, Pajau and Knights, Dan and Hutkins, Robert W. and Walter, Jens},
  year = {2016},
  month = oct,
  volume = {20},
  pages = {515--526},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2016.09.001},
  abstract = {Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30\% of individuals for at least 6~months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B.~longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution.},
  journal = {Cell Host \& Microbe},
  keywords = {喂养菌群,里程碑},
  language = {eng},
  number = {4},
  pmid = {27693307}
}

@article{manichanhReducedDiversityFaecal2006,
  title = {Reduced Diversity of Faecal Microbiota in {{Crohn}}'s Disease Revealed by a Metagenomic Approach},
  author = {Manichanh, C. and {Rigottier-Gois}, L. and Bonnaud, E. and Gloux, K. and Pelletier, E. and Frangeul, L. and Nalin, R. and Jarrin, C. and Chardon, P. and Marteau, P. and Roca, J. and Dore, J.},
  year = {2006},
  month = feb,
  volume = {55},
  pages = {205--211},
  publisher = {{BMJ Publishing Group}},
  issn = {0017-5749, 1468-3288},
  doi = {10.1136/gut.2005.073817},
  abstract = {Background and aim: A role for the intestinal microbial community (microbiota) in the onset and chronicity of Crohn's disease (CD) is strongly suspected. However, investigation of such a complex ecosystem is difficult, even with culture independent molecular approaches. Methods: We used, for the first time, a comprehensive metagenomic approach to investigate the full range of intestinal microbial diversity. We used a fosmid vector to construct two libraries of genomic DNA isolated directly from faecal samples of six healthy donors and six patients with CD. Bacterial diversity was analysed by screening the two DNA libraries, each composed of 25 000 clones, for the 16S rRNA gene by DNA hybridisation. Results: Among 1190 selected clones, we identified 125 non-redundant ribotypes mainly represented by the phyla Bacteroidetes and Firmicutes. Among the Firmicutes, 43 distinct ribotypes were identified in the healthy microbiota, compared with only 13 in CD (p{$<$}0.025). Fluorescent in situ hybridisation directly targeting 16S rRNA in faecal samples analysed individually (n = 12) confirmed the significant reduction in the proportion of bacteria belonging to this phylum in CD patients (p{$<$}0.02). Conclusion: The metagenomic approach allowed us to detect a reduced complexity of the bacterial phylum Firmicutes as a signature of the faecal microbiota in patients with CD. It also indicated the presence of new bacterial species.},
  chapter = {Inflammatory bowel disease},
  copyright = {Copyright 2006 by Gut},
  journal = {Gut},
  language = {en},
  number = {2},
  pmid = {16188921}
}

@article{marchesiHumanColorectalCancer2011,
  title = {Towards the {{Human Colorectal Cancer Microbiome}}},
  author = {Marchesi, Julian R. and Dutilh, Bas E. and Hall, Neil and Peters, Wilbert H. M. and Roelofs, Rian and Boleij, Annemarie and Tjalsma, Harold},
  year = {2011},
  month = may,
  volume = {6},
  pages = {e20447},
  publisher = {{Public Library of Science}},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0020447},
  abstract = {Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.},
  journal = {PLOS ONE},
  language = {en},
  number = {5}
}

@article{martensMucosalGlycanForaging2008,
  title = {Mucosal Glycan Foraging Enhances Fitness and Transmission of a Saccharolytic Human Gut Bacterial Symbiont},
  author = {Martens, Eric C. and Chiang, Herbert C. and Gordon, Jeffrey I.},
  year = {2008},
  month = nov,
  volume = {4},
  pages = {447--457},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2008.09.007},
  abstract = {The distal human gut is a microbial bioreactor that digests complex carbohydrates. The strategies evolved by gut microbes to sense and process diverse glycans have important implications for the assembly and operation of this ecosystem. The human gut-derived bacterium Bacteroides thetaiotaomicron forages on both host and dietary glycans. Its ability to target these substrates resides in 88 polysaccharide utilization loci (PULs), encompassing 18\% of its genome. Whole genome transcriptional profiling and genetic tests were used to define the mechanisms underlying host glycan foraging in vivo and in vitro. PULs that target all major classes of host glycans were identified. However, mucin O-glycans are the principal host substrate foraged in vivo. Simultaneous deletion of five genes encoding ECF-sigma transcription factors, which activate mucin O-glycan utilization, produces defects in bacterial persistence in the gut and in mother-to-offspring transmission. Thus, PUL-mediated glycan catabolism is an important component in gut colonization and may impact microbiota ecology.},
  journal = {Cell Host \& Microbe},
  keywords = {喂养菌群,里程碑},
  language = {eng},
  number = {5},
  pmcid = {PMC2605320},
  pmid = {18996345}
}

@article{mazmanianImmunomodulatoryMoleculeSymbiotic2005,
  title = {An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System},
  author = {Mazmanian, Sarkis K. and Liu, Cui Hua and Tzianabos, Arthur O. and Kasper, Dennis L.},
  year = {2005},
  month = jul,
  volume = {122},
  pages = {107--118},
  issn = {0092-8674},
  doi = {10.1016/j.cell.2005.05.007},
  abstract = {The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.},
  journal = {Cell},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {1},
  pmid = {16009137}
}

@article{mazmanianMicrobialSymbiosisFactor2008,
  title = {A Microbial Symbiosis Factor Prevents Intestinal Inflammatory Disease},
  author = {Mazmanian, Sarkis K. and Round, June L. and Kasper, Dennis L.},
  year = {2008},
  month = may,
  volume = {453},
  pages = {620--625},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature07008},
  abstract = {Bacteroides fragilis is a member of the human intestinal microbiota. It is reported that a single molecule produced by this bacterium, polysaccharide A, can suppress the intestinal inflammatory response and thus protect from experimental colitis.},
  copyright = {2008 Nature Publishing Group},
  journal = {Nature},
  keywords = {粘膜免疫,里程碑},
  language = {en},
  number = {7195}
}

@article{mehtaStabilityHumanFaecal2018,
  title = {Stability of the Human Faecal Microbiome in a Cohort of Adult Men},
  author = {Mehta, Raaj S. and {Abu-Ali}, Galeb S. and Drew, David A. and {Lloyd-Price}, Jason and Subramanian, Ayshwarya and Lochhead, Paul and Joshi, Amit D. and Ivey, Kerry L. and Khalili, Hamed and Brown, Gordon T. and DuLong, Casey and Song, Mingyang and Nguyen, Long H. and Mallick, Himel and Rimm, Eric B. and Izard, Jacques and Huttenhower, Curtis and Chan, Andrew T.},
  year = {2018},
  month = mar,
  volume = {3},
  pages = {347--355},
  issn = {2058-5276},
  doi = {10.1038/s41564-017-0096-0},
  abstract = {Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples-one pair collected 24-72\,h apart and a second pair \textasciitilde 6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for \textasciitilde 74\% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics.},
  journal = {Nature Microbiology},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC6016839},
  pmid = {29335554}
}

@article{mellEvidenceLinkGut2015,
  title = {Evidence for a Link between Gut Microbiota and Hypertension in the {{Dahl}} Rat},
  author = {Mell, Blair and Jala, Venkatakrishna R. and Mathew, Anna V. and Byun, Jaeman and Waghulde, Harshal and Zhang, Youjie and Haribabu, Bodduluri and {Vijay-Kumar}, Matam and Pennathur, Subramaniam and Joe, Bina},
  year = {2015},
  month = mar,
  volume = {47},
  pages = {187--197},
  publisher = {{American Physiological Society}},
  issn = {1094-8341},
  doi = {10.1152/physiolgenomics.00136.2014},
  abstract = {The gut microbiota plays a critical role in maintaining physiological homeostasis. This study was designed to evaluate whether gut microbial composition affects hypertension. 16S rRNA genes obtained from cecal samples of Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats were sequenced. Bacteria of the phylum Bacteroidetes were higher in the S rats compared with the R rats. Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the S rats compared with the R rats. Analyses of the various phylogenetic groups of cecal microbiota revealed significant differences between S and R rats. Both strains were maintained on a high-salt diet, administered antibiotics for ablation of microbiota, transplanted with S or R rat cecal contents, and monitored for blood pressure (BP). Systolic BP of the R rats remained unaltered irrespective of S or R rat cecal transplantation. Surprisingly, compared with the S rats given S rat cecal content, systolic BP of the S rats given a single bolus of cecal content from R rats was consistently and significantly elevated during the rest of their life, and they had a shorter lifespan. A lower level of fecal bacteria of the family Veillonellaceae and increased plasma acetate and heptanoate were features associated with the increased BP observed in the S rats given R rat microbiota compared with the S rats given S rat microbiota. These data demonstrate a link between microbial content and BP regulation and, because the S and R rats differ in their genomic composition, provide the necessary basis to further examine the relationship between the host genome and microbiome in the context of BP regulation in the Dahl rats.},
  journal = {Physiological Genomics},
  number = {6}
}

@misc{MicrobesThatLive,
  title = {The Microbes That Live with Us from Cradle to Grave},
  abstract = {Inside your body there are trillions of microscopic organisms: bacteria, viruses, fungi and archaea - collectively known as the microbiota.  Over the past decade, we've learnt that these communities help to shape our physiology and contribute to our wellbeing.  But there are still many questions: When do we acquire our first microbes? How does our microbiota change throughout our lives and how do these changes differ between people or contribute to disease?    Alongside this animation we have published a series of essays about the human microbiota, which you can read here: https://www.nature.com/collections/bh... This Nature Video is editorially independent. It is produced with third party financial support. Read more about Supported Content here: https://partnerships.nature.com/comme... 18th June 2019}
}

@article{MicrobiotaInfluencesMetabolism2019,
  title = {The Microbiota Influences Metabolism of Host-Directed Drugs},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00052-w},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  keywords = {药物转化,里程碑},
  language = {en}
}

@article{minotHumanGutVirome2011,
  title = {The Human Gut Virome: Inter-Individual Variation and Dynamic Response to Diet},
  shorttitle = {The Human Gut Virome},
  author = {Minot, Samuel and Sinha, Rohini and Chen, Jun and Li, Hongzhe and Keilbaugh, Sue A. and Wu, Gary D. and Lewis, James D. and Bushman, Frederic D.},
  year = {2011},
  month = oct,
  volume = {21},
  pages = {1616--1625},
  issn = {1549-5469},
  doi = {10.1101/gr.122705.111},
  abstract = {Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human "virome") in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet.},
  journal = {Genome Research},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {10},
  pmcid = {PMC3202279},
  pmid = {21880779}
}

@article{mueggeDietDrivesConvergence2011,
  title = {Diet {{Drives Convergence}} in {{Gut Microbiome Functions Across Mammalian Phylogeny}} and {{Within Humans}}},
  author = {Muegge, Brian D. and Kuczynski, Justin and Knights, Dan and Clemente, Jose C. and Gonz{\'a}lez, Antonio and Fontana, Luigi and Henrissat, Bernard and Knight, Rob and Gordon, Jeffrey I.},
  year = {2011},
  month = may,
  volume = {332},
  pages = {970--974},
  publisher = {{American Association for the Advancement of Science}},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.1198719},
  abstract = {Coevolution of mammals and their gut microbiota has profoundly affected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S ribosomal RNA genes to gain an understanding of how microbial communities adapt to extremes of diet. We sampled fecal DNA from 33 mammalian species and 18 humans who kept detailed diet records, and we found that the adaptation of the microbiota to diet is similar across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to understand host evolutionary histories at a supraorganismal level. The normal range of physiological and metabolic phenotypes has been shaped by coevolution with microbial symbionts. The normal range of physiological and metabolic phenotypes has been shaped by coevolution with microbial symbionts.},
  chapter = {Report},
  copyright = {Copyright \textcopyright{} 2011, American Association for the Advancement of Science},
  journal = {Science},
  language = {en},
  number = {6032},
  pmid = {21596990}
}

@article{murriGutMicrobiotaChildren2013,
  title = {Gut Microbiota in Children with Type 1 Diabetes Differs from That in Healthy Children: A Case-Control Study},
  shorttitle = {Gut Microbiota in Children with Type 1 Diabetes Differs from That in Healthy Children},
  author = {Murri, Mora and Leiva, Isabel and {Gomez-Zumaquero}, Juan Miguel and Tinahones, Francisco J. and Cardona, Fernando and Soriguer, Federico and {Queipo-Ortu{\~n}o}, Mar{\'i}a Isabel},
  year = {2013},
  month = feb,
  volume = {11},
  pages = {46},
  issn = {1741-7015},
  doi = {10.1186/1741-7015-11-46},
  abstract = {A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.},
  journal = {BMC Medicine},
  number = {1}
}

@article{naikCompartmentalizedControlSkin2012,
  title = {Compartmentalized Control of Skin Immunity by Resident Commensals},
  author = {Naik, Shruti and Bouladoux, Nicolas and Wilhelm, Christoph and Molloy, Michael J. and Salcedo, Rosalba and Kastenmuller, Wolfgang and Deming, Clayton and Quinones, Mariam and Koo, Lily and Conlan, Sean and Spencer, Sean and Hall, Jason A. and Dzutsev, Amiran and Kong, Heidi and Campbell, Daniel J. and Trinchieri, Giorgio and Segre, Julia A. and Belkaid, Yasmine},
  year = {2012},
  month = aug,
  volume = {337},
  pages = {1115--1119},
  issn = {1095-9203},
  doi = {10.1126/science.1225152},
  abstract = {Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.},
  journal = {Science (New York, N.Y.)},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {6098},
  pmcid = {PMC3513834},
  pmid = {22837383}
}

@misc{NatureChuPinRenTiJunQunYanJiuDeLiChengBeiShang,
  title = {{{Nature出品}}：人体菌群研究的里程碑（上）-热心肠日报},
  abstract = {中国最大的肠道专业知识库，2019年底将发布1300期。},
  howpublished = {https://www.mr-gut.cn/daily/show/1234290001}
}

@misc{NatureChuPinRenTiJunQunYanJiuDeLiChengBeiXia,
  title = {{{Nature出品}}：人体菌群研究的里程碑（下）-热心肠日报},
  abstract = {中国最大的肠道专业知识库，2019年底将发布1300期。},
  howpublished = {https://www.mr-gut.cn/daily/show/1270351010?kf=read}
}

@misc{NatureRenTiJunQunYanJiuLiChengBeiWeiYangChangDaoJunQunReXinChangRiBao,
  title = {{{Nature人体菌群研究里程碑}}：喂养肠道菌群-热心肠日报},
  abstract = {中国最大的肠道专业知识库，2019年底将发布1300期。},
  howpublished = {https://www.mr-gut.cn/papers/read/1046917499},
  keywords = {喂养菌群,里程碑}
}

@article{normanDiseasespecificAlterationsEnteric2015,
  title = {Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease},
  author = {Norman, Jason M. and Handley, Scott A. and Baldridge, Megan T. and Droit, Lindsay and Liu, Catherine Y. and Keller, Brian C. and Kambal, Amal and Monaco, Cynthia L. and Zhao, Guoyan and Fleshner, Phillip and Stappenbeck, Thaddeus S. and McGovern, Dermot P. B. and Keshavarzian, Ali and Mutlu, Ece A. and Sauk, Jenny and Gevers, Dirk and Xavier, Ramnik J. and Wang, David and Parkes, Miles and Virgin, Herbert W.},
  year = {2015},
  month = jan,
  volume = {160},
  pages = {447--460},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2015.01.002},
  abstract = {Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.},
  journal = {Cell},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC4312520},
  pmid = {25619688}
}

@article{omahonyCommensalinducedRegulatoryCells2008,
  title = {Commensal-Induced Regulatory {{T}} Cells Mediate Protection against Pathogen-Stimulated {{NF}}-{{kappaB}} Activation},
  author = {O'Mahony, Caitlin and Scully, Paul and O'Mahony, David and Murphy, Sharon and O'Brien, Frances and Lyons, Anne and Sherlock, Graham and MacSharry, John and Kiely, Barry and Shanahan, Fergus and O'Mahony, Liam},
  year = {2008},
  month = aug,
  volume = {4},
  pages = {e1000112},
  issn = {1553-7374},
  doi = {10.1371/journal.ppat.1000112},
  abstract = {Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-kappaB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-kappaB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to na\"ive animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-kappaB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis-fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-kappaB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-kappaB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.},
  journal = {PLoS pathogens},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {8},
  pmcid = {PMC2474968},
  pmid = {18670628}
}

@article{OriginsHumanMicrobiota2019,
  title = {The Origins of Human Microbiota Research},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00073-5},
  abstract = {Research into human-associated microbiota has come a long way since Antonie van Leeuwenhoek first began to study microorganisms back in the 17th century. What advances allowed researchers to move from seeing single cells to studying complex microbial communities? In this audio, we hear from microbiologist David Relman, who spoke with Anand Jagatia.},
  copyright = {2019 Nature},
  journal = {Nature Research},
  language = {en}
}

@article{palmerDevelopmentHumanInfant2007,
  title = {Development of the Human Infant Intestinal Microbiota},
  author = {Palmer, Chana and Bik, Elisabeth M. and DiGiulio, Daniel B. and Relman, David A. and Brown, Patrick O.},
  year = {2007},
  month = jul,
  volume = {5},
  pages = {e177},
  issn = {1545-7885},
  doi = {10.1371/journal.pbio.0050177},
  abstract = {Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.},
  journal = {PLoS biology},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {7},
  pmcid = {PMC1896187},
  pmid = {17594176}
}

@article{pamerResurrectingIntestinalMicrobiota2016,
  title = {Resurrecting the Intestinal Microbiota to Combat Antibiotic-Resistant Pathogens},
  author = {Pamer, E. G.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {535--538},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad9382},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{parienteFieldBorn2019,
  title = {A Field Is Born},
  author = {Pariente, Nonia},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00006-2},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  language = {en}
}

@article{peiBacterialBiotaHuman2004,
  title = {Bacterial Biota in the Human Distal Esophagus},
  author = {Pei, Zhiheng and Bini, Edmund J. and Yang, Liying and Zhou, Meisheng and Francois, Fritz and Blaser, Martin J.},
  year = {2004},
  month = mar,
  volume = {101},
  pages = {4250},
  publisher = {{National Academy of Sciences}},
  doi = {10.1073/pnas.0306398101},
  abstract = {The esophagus, like other luminal organs of the digestive system, provides a potential environment for bacterial colonization, but little is known about the presence of a bacterial biota or its nature. By using broad-range 16S rDNA PCR, biopsies were ...},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {技术进步,里程碑},
  language = {en},
  number = {12},
  pmid = {15016918}
}

@article{qinHumanGutMicrobial2010a,
  title = {A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing},
  author = {Qin, Junjie and Li, Ruiqiang and Raes, Jeroen and Arumugam, Manimozhiyan and Burgdorf, Kristoffer Solvsten and Manichanh, Chaysavanh and Nielsen, Trine and Pons, Nicolas and Levenez, Florence and Yamada, Takuji and Mende, Daniel R. and Li, Junhua and Xu, Junming and Li, Shaochuan and Li, Dongfang and Cao, Jianjun and Wang, Bo and Liang, Huiqing and Zheng, Huisong and Xie, Yinlong and Tap, Julien and Lepage, Patricia and Bertalan, Marcelo and Batto, Jean-Michel and Hansen, Torben and Le Paslier, Denis and Linneberg, Allan and Nielsen, H. Bj{\o}rn and Pelletier, Eric and Renault, Pierre and {Sicheritz-Ponten}, Thomas and Turner, Keith and Zhu, Hongmei and Yu, Chang and Li, Shengting and Jian, Min and Zhou, Yan and Li, Yingrui and Zhang, Xiuqing and Li, Songgang and Qin, Nan and Yang, Huanming and Wang, Jian and Brunak, S{\o}ren and Dor{\'e}, Joel and Guarner, Francisco and Kristiansen, Karsten and Pedersen, Oluf and Parkhill, Julian and Weissenbach, Jean and Bork, Peer and Ehrlich, S. Dusko and Wang, Jun},
  year = {2010},
  month = mar,
  volume = {464},
  pages = {59--65},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature08821},
  abstract = {To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, {$\sim$}150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99\% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.},
  copyright = {2010 The Author(s)},
  journal = {Nature},
  language = {en},
  number = {7285}
}

@article{qinMetagenomewideAssociationStudy2012b,
  title = {A Metagenome-Wide Association Study of Gut Microbiota in Type 2 Diabetes},
  author = {Qin, Junjie and Li, Yingrui and Cai, Zhiming and Li, Shenghui and Zhu, Jianfeng and Zhang, Fan and Liang, Suisha and Zhang, Wenwei and Guan, Yuanlin and Shen, Dongqian and Peng, Yangqing and Zhang, Dongya and Jie, Zhuye and Wu, Wenxian and Qin, Youwen and Xue, Wenbin and Li, Junhua and Han, Lingchuan and Lu, Donghui and Wu, Peixian and Dai, Yali and Sun, Xiaojuan and Li, Zesong and Tang, Aifa and Zhong, Shilong and Li, Xiaoping and Chen, Weineng and Xu, Ran and Wang, Mingbang and Feng, Qiang and Gong, Meihua and Yu, Jing and Zhang, Yanyan and Zhang, Ming and Hansen, Torben and Sanchez, Gaston and Raes, Jeroen and Falony, Gwen and Okuda, Shujiro and Almeida, Mathieu and LeChatelier, Emmanuelle and Renault, Pierre and Pons, Nicolas and Batto, Jean-Michel and Zhang, Zhaoxi and Chen, Hua and Yang, Ruifu and Zheng, Weimou and Li, Songgang and Yang, Huanming and Wang, Jian and Ehrlich, S. Dusko and Nielsen, Rasmus and Pedersen, Oluf and Kristiansen, Karsten and Wang, Jun},
  year = {2012},
  month = oct,
  volume = {490},
  pages = {55--60},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature11450},
  abstract = {Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.},
  copyright = {2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7418}
}

@article{rajilic-stojanovicLongtermMonitoringHuman2012,
  title = {Long-Term Monitoring of the Human Intestinal Microbiota Composition},
  author = {{Rajili{\'c}-Stojanovi{\'c}}, Mirjana and Heilig, Hans G. H. J. and Tims, Sebastian and Zoetendal, Erwin G. and {de Vos}, Willem M.},
  year = {2012},
  month = oct,
  issn = {1462-2920},
  doi = {10.1111/1462-2920.12023},
  abstract = {The microbiota that colonizes the human intestinal tract is complex and its structure is specific for each of us. In this study we expand the knowledge about the stability of the subject-specific microbiota and show that this ecosystem is stable in short-term intervals ({$<$}\,1 year) but also during long periods of time ({$>$}\,10 years). The faecal microbiota composition of five unrelated and healthy subjects was analysed using a comprehensive and highly reproducible phylogenetic microarray, the HITChip. The results show that the use of antibiotics, application of specific dietary regimes and distant travelling have limited impact on the microbiota composition. Several anaerobic genera, including Bifidobacterium and a number of genera within the Bacteroidetes and the Firmicutes phylum, exhibit significantly higher similarity than the total microbiota. Although the gut microbiota contains subject-specific species, the presence of which is preserved throughout the years, their relative abundance changes considerably. Consequently, the recently proposed enterotype status appears to be a varying characteristic of the microbiota. Our data show that the intestinal microbiota contains a core community of permanent colonizers, and that environmentally introduced changes of the microbiota throughout adulthood are primarily affecting the abundance but not the presence of specific microbial species.},
  journal = {Environmental Microbiology},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  pmid = {23286720}
}

@article{rakoff-nahoumRecognitionCommensalMicroflora2004,
  title = {Recognition of {{Commensal Microflora}} by {{Toll}}-{{Like Receptors Is Required}} for {{Intestinal Homeostasis}}},
  author = {{Rakoff-Nahoum}, Seth and Paglino, Justin and {Eslami-Varzaneh}, Fatima and Edberg, Stephen and Medzhitov, Ruslan},
  year = {2004},
  month = jul,
  volume = {118},
  pages = {229--241},
  publisher = {{Elsevier}},
  issn = {0092-8674, 1097-4172},
  doi = {10.1016/j.cell.2004.07.002},
  journal = {Cell},
  language = {English},
  number = {2},
  pmid = {15260992}
}

@article{ramananHelminthInfectionPromotes2016,
  title = {Helminth Infection Promotes Colonization Resistance via Type 2 Immunity},
  author = {Ramanan, D. and Bowcutt, R. and Lee, S. C. and Tang, M. S. and Kurtz, Z. D. and Ding, Y. and Honda, K. and Gause, W. C. and Blaser, M. J. and Bonneau, R. A. and Lim, Y. A. L. and Loke, P. and Cadwell, K.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {608--612},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aaf3229},
  journal = {Science},
  language = {en},
  number = {6285}
}

@misc{ReXinChangXianSheng62ZhangHuanDengZongLan,
  title = {热心肠先生：62 张幻灯纵览 2019 年肠道故事和研究大势},
  abstract = {热心肠研究院致力于链接肠道领域的学者、医生、企业家、政府和媒体人士，为受众提供包括在线知识库、落地活动、科普自媒体内容等在内的多项满足行业需求的服务。},
  howpublished = {https://www.mr-gut.cn/articles/ss/7758b66b71d2435681189b10a8d7149f?kf=rxcyjy}
}

@article{reyesVirusesFaecalMicrobiota2010,
  title = {Viruses in the Faecal Microbiota of Monozygotic Twins and Their Mothers},
  author = {Reyes, Alejandro and Haynes, Matthew and Hanson, Nicole and Angly, Florent E. and Heath, Andrew C. and Rohwer, Forest and Gordon, Jeffrey I.},
  year = {2010},
  month = jul,
  volume = {466},
  pages = {334--338},
  issn = {1476-4687},
  doi = {10.1038/nature09199},
  abstract = {Viral diversity and life cycles are poorly understood in the human gut and other body habitats. Phages and their encoded functions may provide informative signatures of a human microbiota and of microbial community responses to various disturbances, and may indicate whether community health or dysfunction is manifest after apparent recovery from a disease or therapeutic intervention. Here we report sequencing of the viromes (metagenomes) of virus-like particles isolated from faecal samples collected from healthy adult female monozygotic twins and their mothers at three time points over a one-year period. We compared these data sets with data sets of sequenced bacterial 16S ribosomal RNA genes and total-faecal-community DNA. Co-twins and their mothers share a significantly greater degree of similarity in their faecal bacterial communities than do unrelated individuals. In contrast, viromes are unique to individuals regardless of their degree of genetic relatedness. Despite remarkable interpersonal variations in viromes and their encoded functions, intrapersonal diversity is very low, with {$>$}95\% of virotypes retained over the period surveyed, and with viromes dominated by a few temperate phages that exhibit remarkable genetic stability. These results indicate that a predatory viral-microbial dynamic, manifest in a number of other characterized environmental ecosystems, is notably absent in the very distal intestine.},
  journal = {Nature},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {7304},
  pmcid = {PMC2919852},
  pmid = {20631792}
}

@article{ridauraGutMicrobiotaTwins2013a,
  ids = {ridauraGutMicrobiotaTwins2013},
  title = {Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice},
  author = {Ridaura, Vanessa K. and Faith, Jeremiah J. and Rey, Federico E. and Cheng, Jiye and Duncan, Alexis E. and Kau, Andrew L. and Griffin, Nicholas W. and Lombard, Vincent and Henrissat, Bernard and Bain, James R. and Muehlbauer, Michael J. and Ilkayeva, Olga and Semenkovich, Clay F. and Funai, Katsuhiko and Hayashi, David K. and Lyle, Barbara J. and Martini, Margaret C. and Ursell, Luke K. and Clemente, Jose C. and Van Treuren, William and Walters, William A. and Knight, Rob and Newgard, Christopher B. and Heath, Andrew C. and Gordon, Jeffrey I.},
  year = {2013},
  month = sep,
  volume = {341},
  pages = {1241214},
  issn = {1095-9203},
  doi = {10.1126/science.1241214},
  abstract = {The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.},
  journal = {Science (New York, N.Y.)},
  keywords = {Adiposity,Adult,Animals,Bacteroidetes,Cecum,Diet; Fat-Restricted,Feces,Female,Gastrointestinal Tract,Germ-Free Life,Humans,Metabolome,Metagenome,Mice,Mice; Inbred C57BL,Mice; Obese,Obesity,Thinness,Twins,Weight Gain,Young Adult},
  language = {eng},
  number = {6150},
  pmcid = {PMC3829625},
  pmid = {24009397}
}

@article{rohwerProductionShotgunLibraries2001,
  title = {Production of Shotgun Libraries Using Random Amplification},
  author = {Rohwer, F. and Seguritan, V. and Choi, D. H. and Segall, A. M. and Azam, F.},
  year = {2001},
  month = jul,
  volume = {31},
  pages = {108--112, 114--116, 118},
  issn = {0736-6205},
  doi = {10.2144/01311rr02},
  abstract = {In the following report, thermal cycling coupled with random 10-mers as primers was used to construct randomly amplified shotgun libraries (RASLs). This approach allowed shotgun libraries to be constructed from nanogram quantities of input DNA. RASLs contained inserts from throughout a target genome in an unbiased fashion and did not appear to contain chimeric sequences. This protocol should be useful for shotgun sequencing the genomes of unculturable organisms and rapidly producing shotgun libraries from cosmids, fosmids, yeast artificial chromosomes (YACs), and bacterial artificial chromosomes (BACs).},
  journal = {BioTechniques},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {1},
  pmid = {11464504}
}

@article{romanoIntestinalMicrobiotaComposition2015,
  title = {Intestinal {{Microbiota Composition Modulates Choline Bioavailability}} from {{Diet}} and {{Accumulation}} of the {{Proatherogenic Metabolite Trimethylamine}}-{{N}}-{{Oxide}}},
  author = {Romano, Kymberleigh A. and Vivas, Eugenio I. and {Amador-Noguez}, Daniel and Rey, Federico E.},
  year = {2015},
  month = may,
  volume = {6},
  publisher = {{American Society for Microbiology}},
  issn = {2150-7511},
  doi = {10.1128/mBio.02481-14},
  abstract = {Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.},
  chapter = {Research Article},
  copyright = {Copyright \textcopyright{} 2015 Romano et al.. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.},
  journal = {mBio},
  language = {en},
  number = {2},
  pmid = {25784704}
}

@misc{SafetyEfficacyFMT,
  title = {Safety and {{Efficacy}} of {{FMT}} in {{Individuals With One}} or {{More Recurrences}} of {{Clostridium Difficile Associated Disease}} ({{CDAD}}) - {{Full Text View}} - {{ClinicalTrials}}.Gov},
  abstract = {Safety and Efficacy of FMT in Individuals With One or More Recurrences of Clostridium Difficile Associated Disease (CDAD) - Full Text View.},
  howpublished = {https://clinicaltrials.gov/ct2/show/NCT03548051},
  keywords = {粪菌移植,里程碑},
  language = {en}
}

@article{sampsonControlBrainDevelopment2015,
  title = {Control of {{Brain Development}}, {{Function}}, and {{Behavior}} by the {{Microbiome}}},
  author = {Sampson, Timothy R. and Mazmanian, Sarkis K.},
  year = {2015},
  month = may,
  volume = {17},
  pages = {565--576},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.04.011},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{satokariDiversityBifidobacteriumLactobacillus2002,
  title = {Diversity of {{Bifidobacterium}} and {{Lactobacillus}} Spp. in {{Breast}}-{{Fed}} and {{Formula}}-{{Fed Infants}} as {{Assessed}} by {{16S rDNA Sequence Differences}}},
  author = {Satokari, Reetta M. and Vaughan, Elaine E. and Favier, Christine F. and Dor{\'e}, Jo{\"e}l and Edwards, Christine and de Vos, Willem M.},
  year = {2002},
  month = jan,
  volume = {14},
  pages = {97--105},
  publisher = {{Taylor \& Francis}},
  issn = {null},
  doi = {10.1080/08910600260081748},
  abstract = {A qualitative molecular monitoring approach based on PCR and denaturing gradient gel electrophoresis (DGGE) was used to study the diversity of dominant bacteria, bifidobacteria and lactobacilli in vaginally delivered full-term infants. Seven breast-fed and six formula-fed infants participated in the study. 16S rDNA targeted primers were used for the specific PCR amplification of fragments from bacteria, bifidobacteria and lactobacilli from faecal samples that were collected before and after weaning at the age of approximately 1 and 7 months, respectively. The PCR fragments were subsequently resolved in a sequence-dependent manner by DGGE. In addition, cloning and sequence analysis of the PCR fragments was used to identify the species from which they originated. Based on the number of fragments in the DGGE profiles it was estimated that breast-fed and formula-fed infants harboured bacterial communities of equal complexity. There was no conspicuous difference in the distribution of Bifidobacterium or Lactobacillus species between breast-fed and formula-fed infants. The most frequently found representatives of these genera were B. infantis and species belonging to the L. acidophilus -group in both groups of infants. The predominant Bifidobacterium and Lactobacillus populations in most infants consisted of only one or two species.},
  annotation = {\_eprint: https://doi.org/10.1080/08910600260081748},
  journal = {Microbial Ecology in Health and Disease},
  keywords = {菌群发育,里程碑},
  number = {2}
}

@article{schefferCatastrophicShiftsEcosystems2001,
  title = {Catastrophic Shifts in Ecosystems},
  author = {Scheffer, Marten and Carpenter, Steve and Foley, Jonathan A. and Folke, Carl and Walker, Brian},
  year = {2001},
  month = oct,
  volume = {413},
  pages = {591--596},
  issn = {0028-0836},
  doi = {10.1038/35098000},
  abstract = {All ecosystems are exposed to gradual changes in climate, nutrient loading, habitat fragmentation or biotic exploitation. Nature is usually assumed to respond to gradual change in a smooth way. However, studies on lakes, coral reefs, oceans, forests and arid lands have shown that smooth change can be interrupted by sudden drastic switches to a contrasting state. Although diverse events can trigger such shifts, recent studies show that a loss of resilience usually paves the way for a switch to an alternative state. This suggests that strategies for sustainable management of such ecosystems should focus on maintaining resilience.},
  copyright = {\textcopyright{} 2001 Nature Publishing Group},
  file = {E\:\\zotero.storage.2016\\Nature\\2001\\Nature_2001_Catastrophic shifts in ecosystems.pdf},
  journal = {Nature},
  language = {en},
  number = {6856}
}

@article{schloissnigGenomicVariationLandscape2013,
  title = {Genomic Variation Landscape of the Human Gut Microbiome},
  author = {Schloissnig, Siegfried and Arumugam, Manimozhiyan and Sunagawa, Shinichi and Mitreva, Makedonka and Tap, Julien and Zhu, Ana and Waller, Alison and Mende, Daniel R. and Kultima, Jens Roat and Martin, John and Kota, Karthik and Sunyaev, Shamil R. and Weinstock, George M. and Bork, Peer},
  year = {2013},
  month = jan,
  volume = {493},
  pages = {45--50},
  issn = {1476-4687},
  doi = {10.1038/nature11711},
  abstract = {Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.},
  journal = {Nature},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {7430},
  pmcid = {PMC3536929},
  pmid = {23222524}
}

@article{schochNuclearRibosomalInternal2012,
  title = {Nuclear Ribosomal Internal Transcribed Spacer ({{ITS}}) Region as a Universal {{DNA}} Barcode Marker for {{Fungi}}},
  author = {Schoch, Conrad L. and Seifert, Keith A. and Huhndorf, Sabine and Robert, Vincent and Spouge, John L. and Levesque, C. Andr{\'e} and Chen, Wen and {Fungal Barcoding Consortium} and {Fungal Barcoding Consortium Author List}},
  year = {2012},
  month = apr,
  volume = {109},
  pages = {6241--6246},
  issn = {1091-6490},
  doi = {10.1073/pnas.1117018109},
  abstract = {Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {16},
  pmcid = {PMC3341068},
  pmid = {22454494}
}

@article{senderAreWeReally2016,
  title = {Are {{We Really Vastly Outnumbered}}? {{Revisiting}} the {{Ratio}} of {{Bacterial}} to {{Host Cells}} in {{Humans}}},
  shorttitle = {Are {{We Really Vastly Outnumbered}}?},
  author = {Sender, Ron and Fuchs, Shai and Milo, Ron},
  year = {2016},
  month = jan,
  volume = {164},
  pages = {337--340},
  issn = {0092-8674},
  doi = {10.1016/j.cell.2016.01.013},
  abstract = {It is often presented as common knowledge that, in the human body, bacteria outnumber human cells by a ratio of at least 10:1. Revisiting the question, we find that the ratio is much closer to 1:1.},
  file = {E\:\\zotero.storage.2016\\2016\\Cell\\Sender et al_2016_Are We Really Vastly Outnumbered.pdf;E\:\\zotero.storage.2016\\Cell\\2016\\Cell_2016_Are We Really Vastly Outnumbered - Revisiting the Ratio of Bacterial to Host Cells in Humans.pdf},
  journal = {Cell},
  keywords = {重要研究论文},
  language = {English},
  number = {3}
}

@article{senderRevisedEstimatesNumber2016,
  title = {Revised {{Estimates}} for the {{Number}} of {{Human}} and {{Bacteria Cells}} in the {{Body}}},
  author = {Sender, Ron and Fuchs, Shai and Milo, Ron},
  year = {2016},
  month = aug,
  volume = {14},
  pages = {e1002533},
  issn = {1545-7885},
  doi = {10.1371/journal.pbio.1002533},
  abstract = {Thoroughly revised estimates show that the typical adult human body consists of about 30 trillion human cells and about 38 trillion bacteria.},
  file = {E\:\\zotero.storage.2016\\2016\\PLOS Biology\\Sender et al_2016_Revised Estimates for the Number of Human and Bacteria Cells in the Body.pdf},
  journal = {PLOS Biology},
  keywords = {重要研究论文},
  number = {8}
}

@article{shaoCommensalCandidaAlbicans2019,
  title = {Commensal {{Candida}} Albicans {{Positively Calibrates Systemic Th17 Immunological Responses}}},
  author = {Shao, Tzu-Yu and Ang, W. X. Gladys and Jiang, Tony T. and Huang, Felicia Scaggs and Andersen, Heidi and Kinder, Jeremy M. and Pham, Giang and Burg, Ashley R. and Ruff, Brandy and Gonzalez, Tammy and Khurana Hershey, Gurjit K. and Haslam, David B. and Way, Sing Sing},
  year = {2019},
  month = mar,
  volume = {25},
  pages = {404-417.e6},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2019.02.004},
  abstract = {Mucosal barriers are densely colonized by pathobiont microbes such as Candida albicans, capable of invasive disseminated infection. However, systemic infections occur infrequently in healthy individuals, suggesting that pathobiont commensalism may elicit host benefits. We show that intestinal colonization with C.~albicans drives systemic expansion of fungal-specific Th17 CD4+ T~cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C.~albicans invasive infection. Protection conferred by commensal C.~albicans requires persistent fungal colonization and extends to other extracellular invasive pathogens such as Staphylococcus aureus. However, commensal C.~albicans does not protect against intracellular influenza virus infection and exacerbates allergic airway inflammation susceptibility, indicating that positively calibrating systemic Th17 responses is not uniformly beneficial. Thus, systemic Th17 inflammation driven by CD4+ T~cells responsive to tonic stimulation by commensal C.~albicans improves host defense against extracellular pathogens, but with potentially harmful immunological consequences.},
  journal = {Cell Host \& Microbe},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC6419754},
  pmid = {30870622}
}

@article{shepherdExclusiveMetabolicNiche2018,
  title = {An Exclusive Metabolic Niche Enables Strain Engraftment in the Gut Microbiota},
  author = {Shepherd, Elizabeth Stanley and DeLoache, William C. and Pruss, Kali M. and Whitaker, Weston R. and Sonnenburg, Justin L.},
  year = {2018},
  month = may,
  volume = {557},
  pages = {434--438},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/s41586-018-0092-4},
  abstract = {Finely tuned control of strain engraftment and abundance in the mouse gut microbiota was achieved using the marine polysaccharide porphyran, which could exclusively be used by an introduced subset of wild-type or genetically modified Bacteroides strains.},
  copyright = {2018 Macmillan Publishers Ltd., part of Springer Nature},
  journal = {Nature},
  keywords = {喂养菌群,里程碑},
  language = {en},
  number = {7705}
}

@article{shinIncreaseAkkermansiaSpp2014,
  title = {An Increase in the {{Akkermansia}} Spp. Population Induced by Metformin Treatment Improves Glucose Homeostasis in Diet-Induced Obese Mice},
  author = {Shin, Na-Ri and Lee, June-Chul and Lee, Hae-Youn and Kim, Min-Soo and Whon, Tae Woong and Lee, Myung-Shik and Bae, Jin-Woo},
  year = {2014},
  month = may,
  volume = {63},
  pages = {727--735},
  publisher = {{BMJ Publishing Group}},
  issn = {0017-5749, 1468-3288},
  doi = {10.1136/gutjnl-2012-303839},
  abstract = {Background Recent evidence indicates that the composition of the gut microbiota contributes to the development of metabolic disorders by affecting the physiology and metabolism of the host. Metformin is one of the most widely prescribed type 2 diabetes (T2D) therapeutic agents. Objective To determine whether the antidiabetic effect of metformin is related to alterations of intestinal microbial composition. Design C57BL/6 mice, fed either a normal-chow diet or a high-fat diet (HFD), were treated with metformin for 6 weeks. The effect of metformin on the composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Adipose tissue inflammation was examined by flow cytometric analysis of the immune cells present in visceral adipose tissue (VAT). Results Metformin treatment significantly improved the glycaemic profile of HFD-fed mice. HFD-fed mice treated with metformin showed a higher abundance of the mucin-degrading bacterium Akkermansia than HFD-fed control mice. In addition, the number of mucin-producing goblet cells was significantly increased by metformin treatment (p{$<$}0.0001). Oral administration of Akkermansia muciniphila to HFD-fed mice without metformin significantly enhanced glucose tolerance and attenuated adipose tissue inflammation by inducing Foxp3 regulatory T cells (Tregs) in the VAT. Conclusions Modulation of the gut microbiota (by an increase in the Akkermansia spp. population) may contribute to the antidiabetic effects of metformin, thereby providing a new mechanism for the therapeutic effect of metformin in patients with T2D. This suggests that pharmacological manipulation of the gut microbiota in favour of Akkermansia may be a potential treatment for T2D.},
  chapter = {Gut microbiota},
  copyright = {Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions},
  journal = {Gut},
  language = {en},
  number = {5},
  pmid = {23804561}
}

@article{smithMicrobialMetabolitesShortChain2013,
  title = {The {{Microbial Metabolites}}, {{Short}}-{{Chain Fatty Acids}}, {{Regulate Colonic Treg Cell Homeostasis}}},
  author = {Smith, Patrick M. and Howitt, Michael R. and Panikov, Nicolai and Michaud, Monia and Gallini, Carey Ann and {Bohlooly-Y}, Mohammad and Glickman, Jonathan N. and Garrett, Wendy S.},
  year = {2013},
  month = aug,
  volume = {341},
  pages = {569--573},
  publisher = {{American Association for the Advancement of Science}},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.1241165},
  abstract = {Protecting the Guts Regulatory T cells (Tregs) in the gut are important sentinels in maintaining the peace between our gut and its trillions of resident bacteria and have been shown to be regulated by specific strains of bacteria in mouse models. Smith et al. (p. 569, published online 4 July; see the Perspective by Bollrath and Powrie) asked whether metabolite(s) generated by resident bacterial species may regulate Tregs in the gut. Indeed, short-chain fatty acids (SCFAs), bacterial fermentation products of dietary fibers produced by a range of bacteria, restored colonic Treg numbers in mice devoid of a gut microbiota and increased Treg numbers in colonized mice. The effects of SCFAs on Tregs were mediated through GPCR43, a receptor for SCFAs, which is expressed on colonic Tregs. Mice fed SCFAs were protected against experimentally induced colitis in a manner that was dependent on GPR43-expressing Tregs. Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota\textendash derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health. Bacterial fermentation products regulate the number and function of regulatory T cells in the mouse colon. [Also see Perspective by Bollrath and Powrie] Bacterial fermentation products regulate the number and function of regulatory T cells in the mouse colon. [Also see Perspective by Bollrath and Powrie]},
  chapter = {Report},
  copyright = {Copyright \textcopyright{} 2013, American Association for the Advancement of Science},
  journal = {Science},
  language = {en},
  number = {6145},
  pmid = {23828891}
}

@article{sobhaniMicrobialDysbiosisColorectal2011,
  title = {Microbial {{Dysbiosis}} in {{Colorectal Cancer}} ({{CRC}}) {{Patients}}},
  author = {Sobhani, Iradj and Tap, Julien and {Roudot-Thoraval}, Fran{\c c}oise and Roperch, Jean P. and Letulle, Sophie and Langella, Philippe and Corthier, G{\'e}rard and Nhieu, Jeanne Tran Van and Furet, Jean P.},
  year = {2011},
  month = jan,
  volume = {6},
  pages = {e16393},
  publisher = {{Public Library of Science}},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0016393},
  abstract = {The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis. Patients and Methods Stool bacterial DNA was extracted prior to colonoscopy from 179 patients: 60 with colorectal cancer, and 119 with normal colonoscopy. Bacterial genes obtained by pyrosequencing of 12 stool samples (6 Normal and 6 Cancer) were subjected to a validated Principal Component Analysis (PCA) test. The dominant and subdominant bacterial population (C. leptum, C. coccoides, Bacteroides/Prevotella, Lactobacillus/Leuconostoc/Pediococcus groups, Bifidobacterium genus, and E. coli, and Faecalibacterium prausnitzii species) were quantified in all individuals using qPCR and specific IL17 producer cells in the intestinal mucosa were characterized using immunohistochemistry. Findings Pyrosequencing (Minimal sequence 200 nucleotide reads) revealed 80\% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software. The phylogenetic core in Cancer individuals was different from that in Normal individuals according to the PCA analysis, with trends towards differences in the dominant and subdominant families of bacteria. Consequently, All-bacteria [log10 (bacteria/g of stool)] in Normal, and Cancer individuals were similar [11.88{$\pm$}0.35, and 11.80{$\pm$}0.56, respectively, (P = 0.16)], according to qPCR values whereas among all dominant and subdominant species only those of Bacteroides/Prevotella were higher (All bacteria-specific bacterium; P = 0.009) in Cancer (-1.04{$\pm$}0.55) than in Normal (-1.40{$\pm$}0.83) individuals. IL17 immunoreactive cells were significantly expressed more in the normal mucosa of cancer patients than in those with normal colonoscopy. Conclusion This is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response. These data open new filed for mass screening and pathophysiology investigations.},
  journal = {PLOS ONE},
  language = {en},
  number = {1}
}

@article{sokolFaecalibacteriumPrausnitziiAntiinflammatory2008,
  title = {Faecalibacterium Prausnitzii Is an Anti-Inflammatory Commensal Bacterium Identified by Gut Microbiota Analysis of {{Crohn}} Disease Patients},
  author = {Sokol, Harry and Pigneur, B{\'e}n{\'e}dicte and Watterlot, Laurie and Lakhdari, Omar and {Berm{\'u}dez-Humar{\'a}n}, Luis G. and Gratadoux, Jean-Jacques and Blugeon, S{\'e}bastien and Bridonneau, Chantal and Furet, Jean-Pierre and Corthier, G{\'e}rard and Grangette, Corinne and Vasquez, Nadia and Pochart, Philippe and Trugnan, Germain and Thomas, Ginette and Blotti{\`e}re, Herv{\'e} M. and Dor{\'e}, Jo{\"e}l and Marteau, Philippe and Seksik, Philippe and Langella, Philippe},
  year = {2008},
  month = oct,
  volume = {105},
  pages = {16731--16736},
  issn = {1091-6490},
  doi = {10.1073/pnas.0804812105},
  abstract = {A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  language = {eng},
  number = {43},
  pmcid = {PMC2575488},
  pmid = {18936492}
}

@article{sokolFungalMicrobiotaDysbiosis2017,
  title = {Fungal Microbiota Dysbiosis in {{IBD}}},
  author = {Sokol, Harry and Leducq, Valentin and Aschard, Hugues and Pham, Hang-Phuong and Jegou, Sarah and Landman, Cecilia and Cohen, David and Liguori, Giuseppina and Bourrier, Anne and {Nion-Larmurier}, Isabelle and Cosnes, Jacques and Seksik, Philippe and Langella, Philippe and Skurnik, David and Richard, Mathias L. and Beaugerie, Laurent},
  year = {2017},
  month = jun,
  volume = {66},
  pages = {1039--1048},
  issn = {1468-3288},
  doi = {10.1136/gutjnl-2015-310746},
  abstract = {OBJECTIVE: The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. DESIGN: Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. RESULTS: We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. CONCLUSIONS: Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.},
  journal = {Gut},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {6},
  pmcid = {PMC5532459},
  pmid = {26843508}
}

@article{sommerResilienceIntestinalMicrobiota2017,
  title = {The Resilience of the Intestinal Microbiota Influences Health and Disease},
  author = {Sommer, Felix and Anderson, Jacqueline Moltzau and Bharti, Richa and Raes, Jeroen and Rosenstiel, Philip},
  year = {2017},
  month = oct,
  volume = {15},
  pages = {630--638},
  issn = {1740-1534},
  doi = {10.1038/nrmicro.2017.58},
  abstract = {The composition of the intestinal microbiota varies among individuals and throughout development, and is dependent on host and environmental factors. However, although the microbiota is constantly exposed to environmental challenges, its composition and function in an individual are stable against perturbations, as microbial communities are resilient and resistant to change. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and also between the microorganisms and the intestinal interface of the host. The resilience of the healthy microbiota protects us from dysbiosis-related diseases, such as inflammatory bowel disease (IBD) or metabolic disorder. By contrast, a resilient dysbiotic microbiota may cause disease. In this Opinion article, we propose that microbial resilience has a key role in health and disease. We will discuss the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health.},
  journal = {Nature Reviews. Microbiology},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {10},
  pmid = {28626231}
}

@article{sonnenburgDietinducedExtinctionsGut2016,
  title = {Diet-Induced Extinctions in the Gut Microbiota Compound over Generations},
  author = {Sonnenburg, Erica D. and Smits, Samuel A. and Tikhonov, Mikhail and Higginbottom, Steven K. and Wingreen, Ned S. and Sonnenburg, Justin L.},
  year = {2016},
  month = jan,
  volume = {529},
  pages = {212--215},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature16504},
  abstract = {In mice on a low microbiota-accessible carbohydrate (MAC) diet, the diversity of the gut microbiota is depleted, and the effect is transferred and compounded over generations; this phenotype is only reversed after supplementation of the missing taxa via faecal microbiota transplantation, suggesting dietary intervention alone may by insufficient at managing diseases characterized by a dysbiotic microbiota.},
  copyright = {2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  keywords = {喂养菌群,里程碑},
  language = {en},
  number = {7585}
}

@article{spanogiannopoulosMicrobialPharmacistsUs2016,
  title = {The Microbial Pharmacists within Us: A Metagenomic View of Xenobiotic Metabolism},
  shorttitle = {The Microbial Pharmacists within Us},
  author = {Spanogiannopoulos, Peter and Bess, Elizabeth N. and Carmody, Rachel N. and Turnbaugh, Peter J.},
  year = {2016},
  month = apr,
  volume = {14},
  pages = {273--287},
  issn = {1740-1534},
  doi = {10.1038/nrmicro.2016.17},
  abstract = {Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within.},
  journal = {Nature Reviews. Microbiology},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {5},
  pmcid = {PMC5243131},
  pmid = {26972811}
}

@article{stewartTemporalDevelopmentGut2018,
  title = {Temporal Development of the Gut Microbiome in Early Childhood from the {{TEDDY}} Study},
  author = {Stewart, Christopher J. and Ajami, Nadim J. and O'Brien, Jacqueline L. and Hutchinson, Diane S. and Smith, Daniel P. and Wong, Matthew C. and Ross, Matthew C. and Lloyd, Richard E. and Doddapaneni, HarshaVardhan and Metcalf, Ginger A. and Muzny, Donna and Gibbs, Richard A. and Vatanen, Tommi and Huttenhower, Curtis and Xavier, Ramnik J. and Rewers, Marian and Hagopian, William and Toppari, Jorma and Ziegler, Anette-G. and She, Jin-Xiong and Akolkar, Beena and Lernmark, Ake and Hyoty, Heikki and Vehik, Kendra and Krischer, Jeffrey P. and Petrosino, Joseph F.},
  year = {2018},
  month = oct,
  volume = {562},
  pages = {583--588},
  issn = {1476-4687},
  doi = {10.1038/s41586-018-0617-x},
  abstract = {The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1-9 such as persistent islet autoimmunity and type 1 diabetes10-12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46~months of age by 16S rRNA gene sequencing (n\,=\,12,005) and metagenomic sequencing (n\,=\,10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.},
  journal = {Nature},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {7728},
  pmcid = {PMC6415775},
  pmid = {30356187}
}

@article{stoneFaecalMicrobiotaTransplantation2019,
  title = {Faecal Microbiota Transplantation for {{Clostridioides}} Difficile Infection},
  author = {Stone, Louise},
  year = {2019},
  month = jun,
  publisher = {{Nature Publishing Group}},
  doi = {10.1038/d42859-019-00008-0},
  abstract = {Discover the world's best science and medicine  | Nature.com},
  copyright = {2019 Nature},
  journal = {Nature Research},
  keywords = {粪菌移植,里程碑},
  language = {en}
}

@article{subramanianPersistentGutMicrobiota2014,
  title = {Persistent Gut Microbiota Immaturity in Malnourished {{Bangladeshi}} Children},
  author = {Subramanian, Sathish and Huq, Sayeeda and Yatsunenko, Tanya and Haque, Rashidul and Mahfuz, Mustafa and Alam, Mohammed A. and Benezra, Amber and DeStefano, Joseph and Meier, Martin F. and Muegge, Brian D. and Barratt, Michael J. and VanArendonk, Laura G. and Zhang, Qunyuan and Province, Michael A. and Petri, William A. and Ahmed, Tahmeed and Gordon, Jeffrey I.},
  year = {2014},
  month = jun,
  volume = {510},
  pages = {417--421},
  issn = {1476-4687},
  doi = {10.1038/nature13421},
  abstract = {Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.},
  journal = {Nature},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {7505},
  pmcid = {PMC4189846},
  pmid = {24896187}
}

@article{tangIntestinalMicrobialMetabolism2013b,
  title = {Intestinal {{Microbial Metabolism}} of {{Phosphatidylcholine}} and {{Cardiovascular Risk}}},
  author = {Tang, W.H. Wilson and Wang, Zeneng and Levison, Bruce S. and Koeth, Robert A. and Britt, Earl B. and Fu, Xiaoming and Wu, Yuping and Hazen, Stanley L.},
  year = {2013},
  month = apr,
  volume = {368},
  pages = {1575--1584},
  issn = {0028-4793, 1533-4406},
  doi = {10.1056/NEJMoa1109400},
  journal = {New England Journal of Medicine},
  language = {en},
  number = {17}
}

@article{tangIntestinalMicrobiotaDependentPhosphatidylcholine2015,
  title = {Intestinal {{Microbiota}}-{{Dependent Phosphatidylcholine Metabolites}}, {{Diastolic Dysfunction}}, and {{Adverse Clinical Outcomes}} in {{Chronic Systolic Heart Failure}}},
  author = {Tang, W. H. Wilson and Wang, Zeneng and Shrestha, Kevin and Borowski, Allen G. and Wu, Yuping and Troughton, Richard W. and Klein, Allan L. and Hazen, Stanley L.},
  year = {2015},
  month = feb,
  volume = {21},
  pages = {91--96},
  publisher = {{Elsevier}},
  issn = {1071-9164, 1532-8414},
  doi = {10.1016/j.cardfail.2014.11.006},
  abstract = {{$<$}h2{$>$}Abstract{$<$}/h2{$><$}h3{$>$}Background{$<$}/h3{$><$}p{$>$}Trimethylamine-\emph{N}-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF).{$<$}/p{$><$}h3{$>$}Methods and Results{$<$}/h3{$><$}p{$>$}In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6\textendash 12.1) {$\mu$}mol/L, 10.9 (8.4\textendash 14.0) {$\mu$}mol/L, and 43.8 (37.1\textendash 53.0) {$\mu$}mol/L, respectively, and were correlated with each other (all \emph{P} {$<$} .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9\textendash 13.2] vs 4.8 [3.4\textendash 9.8] {$\mu$}mol/L; \emph{P} = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7\textendash 14.8] vs 4.7 [3.4\textendash 11.3] {$\mu$}mol/L; \emph{P} = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro\textendash B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95\% CI 1.22\textendash 2.20; \emph{P} = .001), betaine (HR 1.51, 95\% CI 1.10\textendash 2.08; \emph{P} = .01), and TMAO (HR 1.48, 95\% CI 1.10\textendash 1.96; \emph{P} = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95\% CI 1.03\textendash 2.14; \emph{P} = .03).{$<$}/p{$><$}h3{$>$}Conclusion{$<$}/h3{$><$}p{$>$}Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices.{$<$}/p{$>$}},
  journal = {Journal of Cardiac Failure},
  language = {English},
  number = {2},
  pmid = {25459686}
}

@article{tangPrognosticValueElevated2014,
  title = {Prognostic {{Value}} of {{Elevated Levels}} of {{Intestinal Microbe}}-{{Generated Metabolite Trimethylamine}}-{{N}}-{{Oxide}} in {{Patients With Heart Failure}}: {{Refining}} the {{Gut Hypothesis}}},
  shorttitle = {Prognostic {{Value}} of {{Elevated Levels}} of {{Intestinal Microbe}}-{{Generated Metabolite Trimethylamine}}-{{N}}-{{Oxide}} in {{Patients With Heart Failure}}},
  author = {Tang, W. H. Wilson and Wang, Zeneng and Fan, Yiying and Levison, Bruce and Hazen, Jennie E. and Donahue, Lillian M. and Wu, Yuping and Hazen, Stanley L.},
  year = {2014},
  month = nov,
  volume = {64},
  pages = {1908--1914},
  issn = {0735-1097},
  doi = {10.1016/j.jacc.2014.02.617},
  abstract = {Background Altered intestinal function is prevalent in patients with heart failure (HF), but its role in adverse outcomes is unclear. Objectives This study investigated the potential pathophysiological contributions of intestinal microbiota in HF. Methods We examined the relationship between fasting plasma trimethylamine-N-oxide (TMAO) and all-cause mortality over a 5-year follow-up in 720 patients with stable HF. Results The median TMAO level was 5.0 {$\mu$}M, which was higher than in subjects without HF (3.5 {$\mu$}M; p~{$<$} 0.001). There~was modest but significant correlation between TMAO concentrations and B-type natriuretic peptide (BNP) levels (r~=~0.23; p~{$<$} 0.001). Higher plasma TMAO levels were associated with a 3.4-fold increased mortality risk. Following adjustments for traditional risk factors and BNP levels, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio [HR]: 2.2; 95\% CI: 1.42 to 3.43; p~{$<$} 0.001), as well as following the addition of estimated glomerular filtration rate to the model (HR: 1.75; 95\% CI: 1.07 to 2.86; p~{$<$} 0.001). Conclusions High TMAO levels were observed in patients with HF, and elevated TMAO levels portended higher long-term mortality risk independent of traditional risk factors and cardiorenal indexes.},
  journal = {Journal of the American College of Cardiology},
  language = {en},
  number = {18}
}

@article{tangw.h.wilsonGutMicrobiotaDependentTrimethylamine2015,
  title = {Gut {{Microbiota}}-{{Dependent Trimethylamine N}}-{{Oxide}} ({{TMAO}}) {{Pathway Contributes}} to {{Both Development}} of {{Renal Insufficiency}} and {{Mortality Risk}} in {{Chronic Kidney Disease}}},
  author = {{Tang W.H. Wilson} and {Wang Zeneng} and {Kennedy David J.} and {Wu Yuping} and {Buffa Jennifer A.} and {Agatisa-Boyle Brendan} and {Li Xinmin S.} and {Levison Bruce S.} and {Hazen Stanley L.}},
  year = {2015},
  month = jan,
  volume = {116},
  pages = {448--455},
  publisher = {{American Heart Association}},
  doi = {10.1161/CIRCRESAHA.116.305360},
  abstract = {Rationale:Trimethylamine-N-oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, phosphatidylcholine (lecithin), and  l-carnitine, is elevated in chronic kidney diseases (CKD) and associated with coronary artery disease pathogenesis.Objective:To both investigate the clinical prognostic value of TMAO in subjects with versus without CKD, and test the hypothesis that TMAO plays a direct contributory role in the development and progression of renal dysfunction.Methods and Results:We first examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in 521 stable subjects with CKD (estimated glomerular filtration rate, {$<$}60 mL/min per 1.73 m2). Median TMAO level among CKD subjects was 7.9 {$\mu$}mol/L (interquartile range, 5.2\textendash 12.4 {$\mu$}mol/L), which was markedly higher (P{$<$}0.001) than in non-CKD subjects (n=3166). Within CKD subjects, higher (fourth versus first quartile) plasma TMAO level was associated with a 2.8-fold increased mortality risk. After adjustments for traditional risk factors, high-sensitivity C-reactive protein, estimated glomerular filtration rate, elevated TMAO levels remained predictive of 5-year mortality risk (hazard ratio, 1.93; 95\% confidence interval, 1.13\textendash 3.29; P{$<$}0.05). TMAO provided significant incremental prognostic value (net reclassification index, 17.26\%; P{$<$}0.001 and differences in area under receiver operator characteristic curve, 63.26\% versus 65.95\%; P=0.036). Among non-CKD subjects, elevated TMAO levels portend poorer prognosis within cohorts of high and low cystatin C. In animal models, elevated dietary choline or TMAO directly led to progressive renal tubulointerstitial fibrosis and dysfunction.Conclusions:Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival. Chronic dietary exposures that increase TMAO directly contributes to progressive renal fibrosis and dysfunction in animal models.},
  journal = {Circulation Research},
  number = {3}
}

@article{tengPredictionEarlyChildhood2015,
  title = {Prediction of {{Early Childhood Caries}} via {{Spatial}}-{{Temporal Variations}} of {{Oral Microbiota}}},
  author = {Teng, Fei and Yang, Fang and Huang, Shi and Bo, Cunpei and Xu, Zhenjiang Zech and Amir, Amnon and Knight, Rob and Ling, Junqi and Xu, Jian},
  year = {2015},
  month = sep,
  volume = {18},
  pages = {296--306},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.08.005},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {3}
}

@article{teoInfantNasopharyngealMicrobiome2015,
  title = {The {{Infant Nasopharyngeal Microbiome Impacts Severity}} of {{Lower Respiratory Infection}} and {{Risk}} of {{Asthma Development}}},
  author = {Teo, Shu Mei and Mok, Danny and Pham, Kym and Kusel, Merci and Serralha, Michael and Troy, Niamh and Holt, Barbara J. and Hales, Belinda J. and Walker, Michael L. and Hollams, Elysia and Bochkov, Yury A. and Grindle, Kristine and Johnston, Sebastian L. and Gern, James E. and Sly, Peter D. and Holt, Patrick G. and Holt, Kathryn E. and Inouye, Michael},
  year = {2015},
  month = may,
  volume = {17},
  pages = {704--715},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.03.008},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{trompetteGutMicrobiotaMetabolism2014,
  title = {Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis},
  author = {Trompette, Aur{\'e}lien and Gollwitzer, Eva S. and Yadava, Koshika and Sichelstiel, Anke K. and Sprenger, Norbert and {Ngom-Bru}, Catherine and Blanchard, Carine and Junt, Tobias and Nicod, Laurent P. and Harris, Nicola L. and Marsland, Benjamin J.},
  year = {2014},
  month = feb,
  volume = {20},
  pages = {159--166},
  issn = {1546-170X},
  doi = {10.1038/nm.3444},
  abstract = {Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.},
  journal = {Nature Medicine},
  keywords = {喂养菌群,里程碑},
  language = {eng},
  number = {2},
  pmid = {24390308}
}

@article{troseidMicrobiotadependentMetaboliteTrimethylamineNoxide2015,
  title = {Microbiota-Dependent Metabolite Trimethylamine-{{N}}-Oxide Is Associated with Disease Severity and Survival of Patients with Chronic Heart Failure},
  author = {Tr{\o}seid, M. and Ueland, T. and Hov, J. R. and Svardal, A. and Gregersen, I. and Dahl, C. P. and Aakhus, S. and Gude, E. and Bj{\o}rndal, B. and Halvorsen, B. and Karlsen, T. H. and Aukrust, P. and Gullestad, L. and Berge, R. K. and Yndestad, A.},
  year = {2015},
  volume = {277},
  pages = {717--726},
  issn = {1365-2796},
  doi = {10.1111/joim.12328},
  abstract = {Objectives Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF. Design Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant-free survival in the patients with HF were explored. Results Plasma levels of TMAO (P = 0.01), choline (P {$<$} 0.001) and betaine (P {$<$} 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant-free survival: approximately 50\% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio 2.24, 95\% confidence interval 1.28\textendash 3.92, P = 0.005). Conclusions TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.},
  annotation = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.12328},
  copyright = {\textcopyright{} 2014 The Association for the Publication of the Journal of Internal Medicine},
  journal = {Journal of Internal Medicine},
  language = {en},
  number = {6}
}

@article{turnbaughCoreGutMicrobiome2009,
  title = {A Core Gut Microbiome in Obese and Lean Twins},
  author = {Turnbaugh, Peter J. and Hamady, Micah and Yatsunenko, Tanya and Cantarel, Brandi L. and Duncan, Alexis and Ley, Ruth E. and Sogin, Mitchell L. and Jones, William J. and Roe, Bruce A. and Affourtit, Jason P. and Egholm, Michael and Henrissat, Bernard and Heath, Andrew C. and Knight, Rob and Gordon, Jeffrey I.},
  year = {2009},
  month = jan,
  volume = {457},
  pages = {480--484},
  issn = {1476-4687},
  doi = {10.1038/nature07540},
  abstract = {The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).},
  journal = {Nature},
  language = {eng},
  number = {7228},
  pmcid = {PMC2677729},
  pmid = {19043404}
}

@article{turnbaughDietInducedObesityLinked2008,
  title = {Diet-{{Induced Obesity Is Linked}} to {{Marked}} but {{Reversible Alterations}} in the {{Mouse Distal Gut Microbiome}}},
  author = {Turnbaugh, Peter J. and B{\"a}ckhed, Fredrik and Fulton, Lucinda and Gordon, Jeffrey I.},
  year = {2008},
  month = apr,
  volume = {3},
  pages = {213--223},
  publisher = {{Elsevier}},
  issn = {1931-3128},
  doi = {10.1016/j.chom.2008.02.015},
  journal = {Cell Host \& Microbe},
  language = {English},
  number = {4},
  pmid = {18407065}
}

@article{turnbaughEffectDietHuman2009,
  title = {The {{Effect}} of {{Diet}} on the {{Human Gut Microbiome}}: {{A Metagenomic Analysis}} in {{Humanized Gnotobiotic Mice}}},
  shorttitle = {The {{Effect}} of {{Diet}} on the {{Human Gut Microbiome}}},
  author = {Turnbaugh, Peter J. and Ridaura, Vanessa K. and Faith, Jeremiah J. and Rey, Federico E. and Knight, Rob and Gordon, Jeffrey I.},
  year = {2009},
  month = nov,
  volume = {1},
  pages = {6ra14-6ra14},
  publisher = {{American Association for the Advancement of Science}},
  issn = {1946-6234, 1946-6242},
  doi = {10.1126/scitranslmed.3000322},
  abstract = {Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor's microbiota. Switching from a low-fat, plant polysaccharide\textendash rich diet to a high-fat, high-sugar ``Western'' diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle ``clinical trials'' that test the effects of environmental and genetic factors on the gut microbiota and host physiology. A translational medicine pipeline is described where human gut microbial communities and diets are re-created in gnotobiotic mice and the impact on microbe and host is defined using metagenomics. A translational medicine pipeline is described where human gut microbial communities and diets are re-created in gnotobiotic mice and the impact on microbe and host is defined using metagenomics.},
  chapter = {Research Article},
  copyright = {Copyright \textcopyright{} 2009, American Association for the Advancement of Science},
  journal = {Science Translational Medicine},
  language = {en},
  number = {6},
  pmid = {20368178}
}

@article{turnbaughObesityassociatedGutMicrobiome2006a,
  title = {An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest},
  author = {Turnbaugh, Peter J. and Ley, Ruth E. and Mahowald, Michael A. and Magrini, Vincent and Mardis, Elaine R. and Gordon, Jeffrey I.},
  year = {2006},
  month = dec,
  volume = {444},
  pages = {1027--1031},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature05414},
  abstract = {The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an `obese microbiota' results in a significantly greater increase in total body fat than colonization with a `lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.},
  copyright = {2006 Nature Publishing Group},
  journal = {Nature},
  language = {en},
  number = {7122}
}

@article{turnbaughOrganismalGeneticTranscriptional2010,
  title = {Organismal, Genetic, and Transcriptional Variation in the Deeply Sequenced Gut Microbiomes of Identical Twins},
  author = {Turnbaugh, Peter J. and Quince, Christopher and Faith, Jeremiah J. and McHardy, Alice C. and Yatsunenko, Tanya and Niazi, Faheem and Affourtit, Jason and Egholm, Michael and Henrissat, Bernard and Knight, Rob and Gordon, Jeffrey I.},
  year = {2010},
  month = apr,
  volume = {107},
  pages = {7503--7508},
  publisher = {{National Academy of Sciences}},
  issn = {0027-8424, 1091-6490},
  doi = {10.1073/pnas.1002355107},
  abstract = {We deeply sampled the organismal, genetic, and transcriptional diversity in fecal samples collected from a monozygotic (MZ) twin pair and compared the results to 1,095 communities from the gut and other body habitats of related and unrelated individuals. Using a new scheme for noise reduction in pyrosequencing data, we estimated the total diversity of species-level bacterial phylotypes in the 1.2-1.5 million bacterial 16S rRNA reads obtained from each deeply sampled cotwin to be \textasciitilde 800 (35.9\%, 49.1\% detected in both). A combined 1.1 million read 16S rRNA dataset representing 281 shallowly sequenced fecal samples from 54 twin pairs and their mothers contained an estimated 4,018 species-level phylotypes, with each sample having a unique species assemblage (53.4 {$\pm$} 0.6\% and 50.3 {$\pm$} 0.5\% overlap with the deeply sampled cotwins). Of the 134 phylotypes with a relative abundance of {$>$}0.1\% in the combined dataset, only 37 appeared in {$>$}50\% of the samples, with one phylotype in the Lachnospiraceae family present in 99\%. Nongut communities had significantly reduced overlap with the deeply sequenced twins' fecal microbiota (18.3 {$\pm$} 0.3\%, 15.3 {$\pm$} 0.3\%). The MZ cotwins' fecal DNA was deeply sequenced (3.8-6.3 Gbp/sample) and assembled reads were assigned to 25 genus-level phylogenetic bins. Only 17\% of the genes in these bins were shared between the cotwins. Bins exhibited differences in their degree of sequence variation, gene content including the repertoire of carbohydrate active enzymes present within and between twins (e.g., predicted cellulases, dockerins), and transcriptional activities. These results provide an expanded perspective about features that make each of us unique life forms and directions for future characterization of our gut ecosystems.},
  chapter = {Biological Sciences},
  copyright = {\textcopyright{}  . Freely available online through the PNAS open access option.},
  journal = {Proceedings of the National Academy of Sciences},
  language = {en},
  number = {16},
  pmid = {20363958}
}

@article{vangayAntibioticsPediatricDysbiosis2015,
  title = {Antibiotics, {{Pediatric Dysbiosis}}, and {{Disease}}},
  author = {Vangay, Pajau and Ward, Tonya and Gerber, Jeffrey S. and Knights, Dan},
  year = {2015},
  month = may,
  volume = {17},
  pages = {553--564},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.04.006},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{vatanenGenomicVariationStrainspecific2019,
  title = {Genomic Variation and Strain-Specific Functional Adaptation in the Human Gut Microbiome during Early Life},
  author = {Vatanen, Tommi and Plichta, Damian R. and Somani, Juhi and M{\"u}nch, Philipp C. and Arthur, Timothy D. and Hall, Andrew Brantley and Rudolf, Sabine and Oakeley, Edward J. and Ke, Xiaobo and Young, Rachel A. and Haiser, Henry J. and Kolde, Raivo and Yassour, Moran and Luopaj{\"a}rvi, Kristiina and Siljander, Heli and Virtanen, Suvi M. and Ilonen, Jorma and Uibo, Raivo and Tillmann, Vallo and Mokurov, Sergei and Dorshakova, Natalya and Porter, Jeffrey A. and McHardy, Alice C. and L{\"a}hdesm{\"a}ki, Harri and Vlamakis, Hera and Huttenhower, Curtis and Knip, Mikael and Xavier, Ramnik J.},
  year = {2019},
  month = mar,
  volume = {4},
  pages = {470--479},
  issn = {2058-5276},
  doi = {10.1038/s41564-018-0321-5},
  abstract = {The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10\% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.},
  journal = {Nature Microbiology},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {3},
  pmcid = {PMC6384140},
  pmid = {30559407}
}

@article{vierbuchenHumanAssociatedArchaeonMethanosphaera2017,
  title = {The {{Human}}-{{Associated Archaeon Methanosphaera}} Stadtmanae {{Is Recognized}} through {{Its RNA}} and {{Induces TLR8}}-{{Dependent NLRP3 Inflammasome Activation}}},
  author = {Vierbuchen, Tim and Bang, Corinna and Rosigkeit, Hanna and Schmitz, Ruth A. and Heine, Holger},
  year = {2017},
  volume = {8},
  pages = {1535},
  issn = {1664-3224},
  doi = {10.3389/fimmu.2017.01535},
  abstract = {The archaeon Methanosphaera stadtmanae is a member of the gut microbiota; yet, the molecular cross-talk between archaea and the human immune system and its potential contribution to inflammatory diseases has not been evaluated. Although archaea are as bacteria prokaryotes, they form a distinct domain having unique features such as different cell wall structures and membrane lipids. So far, no microbe-associated molecular patterns of archaea which activate innate immune receptors have been identified. By stimulating human myeloid cells with M. stadtmanae and purified archaeal nucleic acids, we identified both the microorganism and its RNA as potent stimuli for the innate immune system. To dissect the recognition and activation pathways induced by M. stadtmanae, human monocytic BLaER1 knockout cells were generated using the CRISPR/Cas9 system targeting components of TLR and inflammasome signaling. While the recognition of M. stadtmanae is mediated by TLR7 and TLR8, activation of the NLRP3 inflammasome depends solely on TLR8 engagement. Notably, this process resembles hallmarks of both the canonical and the recently described alternative inflammasome activation. Thus, we have demonstrated for the first time the specific recognition of and response to an archaeon by human cells at the molecular level.},
  journal = {Frontiers in Immunology},
  keywords = {古菌,里程碑},
  language = {eng},
  pmcid = {PMC5694038},
  pmid = {29181003}
}

@article{vijay-kumarMetabolicSyndromeAltered2010,
  title = {Metabolic {{Syndrome}} and {{Altered Gut Microbiota}} in {{Mice Lacking Toll}}-{{Like Receptor}} 5},
  author = {{Vijay-Kumar}, Matam and Aitken, Jesse D. and Carvalho, Frederic A. and Cullender, Tyler C. and Mwangi, Simon and Srinivasan, Shanthi and Sitaraman, Shanthi V. and Knight, Rob and Ley, Ruth E. and Gewirtz, Andrew T.},
  year = {2010},
  month = apr,
  volume = {328},
  pages = {228--231},
  publisher = {{American Association for the Advancement of Science}},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.1179721},
  abstract = {Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome. The innate immune system may promote metabolic health through effects on gut microbes. The innate immune system may promote metabolic health through effects on gut microbes.},
  chapter = {Report},
  copyright = {Copyright \textcopyright{} 2010, American Association for the Advancement of Science},
  journal = {Science},
  language = {en},
  number = {5975},
  pmid = {20203013}
}

@article{vriezeTransferIntestinalMicrobiota2012,
  title = {Transfer of Intestinal Microbiota from Lean Donors Increases Insulin Sensitivity in Individuals with Metabolic Syndrome},
  author = {Vrieze, Anne and Van Nood, Els and Holleman, Frits and Saloj{\"a}rvi, Jarkko and Kootte, Ruud S. and Bartelsman, Joep F. W. M. and {Dallinga-Thie}, Geesje M. and Ackermans, Mariette T. and Serlie, Mireille J. and Oozeer, Raish and Derrien, Muriel and Druesne, Anne and Van Hylckama Vlieg, Johan E. T. and Bloks, Vincent W. and Groen, Albert K. and Heilig, Hans G. H. J. and Zoetendal, Erwin G. and Stroes, Erik S. and {de Vos}, Willem M. and Hoekstra, Joost B. L. and Nieuwdorp, Max},
  year = {2012},
  month = oct,
  volume = {143},
  pages = {913-916.e7},
  issn = {1528-0012},
  doi = {10.1053/j.gastro.2012.06.031},
  abstract = {Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 {$\mu$}mol/kg/min; P {$<$} .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).},
  journal = {Gastroenterology},
  keywords = {Adult,Alcaligenes faecalis,Bacteroidetes,Blood Glucose,Body Mass Index,Clostridium,Escherichia coli,Eubacterium,Fatty Acids; Volatile,Feces,Humans,Insulin Resistance,Intestine; Small,Male,Metabolic Syndrome,Metagenome,Middle Aged,Oxalobacter formigenes,Statistics; Nonparametric,粪菌移植,里程碑},
  language = {eng},
  number = {4},
  pmid = {22728514}
}

@article{walkerDominantDietresponsiveGroups2011,
  title = {Dominant and Diet-Responsive Groups of Bacteria within the Human Colonic Microbiota},
  author = {Walker, Alan W. and Ince, Jennifer and Duncan, Sylvia H. and Webster, Lucy M. and Holtrop, Grietje and Ze, Xiaolei and Brown, David and Stares, Mark D. and Scott, Paul and Bergerat, Aurore and Louis, Petra and McIntosh, Freda and Johnstone, Alexandra M. and Lobley, Gerald E. and Parkhill, Julian and Flint, Harry J.},
  year = {2011},
  month = feb,
  volume = {5},
  pages = {220--230},
  publisher = {{Nature Publishing Group}},
  issn = {1751-7370},
  doi = {10.1038/ismej.2010.118},
  abstract = {The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at {$>$}98\% identity) of which 26, including 19 cultured species, each accounted for {$>$}1\% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that `blooms' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci) increased in most volunteers on the RS diet, accounting for a mean of 17\% of total bacteria compared with 3.8\% on the NSP diet, whereas the uncultured Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium rectale increased on RS (to mean 10.1\%) but decreased, along with Collinsella aerofaciens, on WL. Inter-individual variation was marked, however, with {$>$}60\% of RS remaining unfermented in two volunteers on the RS diet, compared to {$<$}4\% in the other 12 volunteers; these two individuals also showed low numbers of R-ruminococci ({$<$}1\%). Dietary non-digestible carbohydrate can produce marked changes in the gut microbiota, but these depend on the initial composition of an individual's gut microbiota.},
  copyright = {2011 International Society for Microbial Ecology},
  journal = {The ISME Journal},
  language = {en},
  number = {2}
}

@article{wallaceAlleviatingCancerDrug2010,
  title = {Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme},
  author = {Wallace, Bret D. and Wang, Hongwei and Lane, Kimberly T. and Scott, John E. and Orans, Jillian and Koo, Ja Seol and Venkatesh, Madhukumar and Jobin, Christian and Yeh, Li-An and Mani, Sridhar and Redinbo, Matthew R.},
  year = {2010},
  month = nov,
  volume = {330},
  pages = {831--835},
  issn = {1095-9203},
  doi = {10.1126/science.1191175},
  abstract = {The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial {$\beta$}-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial {$\beta$}-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial {$\beta$}-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.},
  journal = {Science (New York, N.Y.)},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {6005},
  pmcid = {PMC3110694},
  pmid = {21051639}
}

@article{wampachBirthModeAssociated2018,
  title = {Birth Mode Is Associated with Earliest Strain-Conferred Gut Microbiome Functions and Immunostimulatory Potential},
  author = {Wampach, Linda and {Heintz-Buschart}, Anna and Fritz, Jo{\"e}lle V. and {Ramiro-Garcia}, Javier and Habier, Janine and Herold, Malte and Narayanasamy, Shaman and Kaysen, Anne and Hogan, Angela H. and Bindl, Lutz and Bottu, Jean and Halder, Rashi and Sj{\"o}qvist, Conny and May, Patrick and Andersson, Anders F. and {de Beaufort}, Carine and Wilmes, Paul},
  year = {2018},
  month = nov,
  volume = {9},
  pages = {5091},
  issn = {2041-1723},
  doi = {10.1038/s41467-018-07631-x},
  abstract = {The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-{$\alpha$}) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-{$\alpha$} and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.},
  journal = {Nature Communications},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {1},
  pmcid = {PMC6269548},
  pmid = {30504906}
}

@article{wampachColonizationSuccessionHuman2017,
  title = {Colonization and {{Succession}} within the {{Human Gut Microbiome}} by {{Archaea}}, {{Bacteria}}, and {{Microeukaryotes}} during the {{First Year}} of {{Life}}},
  author = {Wampach, Linda and {Heintz-Buschart}, Anna and Hogan, Angela and Muller, Emilie E. L. and Narayanasamy, Shaman and Laczny, Cedric C. and Hugerth, Luisa W. and Bindl, Lutz and Bottu, Jean and Andersson, Anders F. and {de Beaufort}, Carine and Wilmes, Paul},
  year = {2017},
  volume = {8},
  pages = {738},
  issn = {1664-302X},
  doi = {10.3389/fmicb.2017.00738},
  abstract = {Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.},
  journal = {Frontiers in Microbiology},
  keywords = {菌群发育,里程碑},
  language = {eng},
  pmcid = {PMC5411419},
  pmid = {28512451}
}

@article{wangGutFloraMetabolism2011,
  title = {Gut Flora Metabolism of Phosphatidylcholine Promotes Cardiovascular Disease},
  author = {Wang, Zeneng and Klipfell, Elizabeth and Bennett, Brian J. and Koeth, Robert and Levison, Bruce S. and DuGar, Brandon and Feldstein, Ariel E. and Britt, Earl B. and Fu, Xiaoming and Chung, Yoon-Mi and Wu, Yuping and Schauer, Phil and Smith, Jonathan D. and Allayee, Hooman and Tang, W. H. Wilson and DiDonato, Joseph A. and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2011},
  month = apr,
  volume = {472},
  pages = {57--63},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature09922},
  abstract = {Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine\textemdash choline, trimethylamine N-oxide (TMAO) and betaine\textemdash were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.},
  copyright = {2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  language = {en},
  number = {7341}
}

@article{wangNonlethalInhibitionGut2015,
  title = {Non-Lethal {{Inhibition}} of {{Gut Microbial Trimethylamine Production}} for the {{Treatment}} of {{Atherosclerosis}}},
  author = {Wang, Zeneng and Roberts, Adam B. and Buffa, Jennifer A. and Levison, Bruce S. and Zhu, Weifei and Org, Elin and Gu, Xiaodong and Huang, Ying and {Zamanian-Daryoush}, Maryam and Culley, Miranda K. and DiDonato, Anthony J. and Fu, Xiaoming and Hazen, Jennie E. and Krajcik, Daniel and DiDonato, Joseph A. and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2015},
  month = dec,
  volume = {163},
  pages = {1585--1595},
  publisher = {{Elsevier}},
  issn = {0092-8674, 1097-4172},
  doi = {10.1016/j.cell.2015.11.055},
  journal = {Cell},
  language = {English},
  number = {7},
  pmid = {26687352}
}

@article{wangPrognosticValueCholine2014,
  title = {Prognostic Value of Choline and Betaine Depends on Intestinal Microbiota-Generated Metabolite Trimethylamine-{{N}}-Oxide},
  author = {Wang, Zeneng and Tang, W. H. Wilson and Buffa, Jennifer A. and Fu, Xiaoming and Britt, Earl B. and Koeth, Robert A. and Levison, Bruce S. and Fan, Yiying and Wu, Yuping and Hazen, Stanley L.},
  year = {2014},
  month = apr,
  volume = {35},
  pages = {904--910},
  publisher = {{Oxford Academic}},
  issn = {0195-668X},
  doi = {10.1093/eurheartj/ehu002},
  abstract = {AbstractAims.  Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietar},
  journal = {European Heart Journal},
  language = {en},
  number = {14}
}

@article{wangStructuralSegregationGut2012a,
  title = {Structural Segregation of Gut Microbiota between Colorectal Cancer Patients and Healthy Volunteers},
  author = {Wang, Tingting and Cai, Guoxiang and Qiu, Yunping and Fei, Na and Zhang, Menghui and Pang, Xiaoyan and Jia, Wei and Cai, Sanjun and Zhao, Liping},
  year = {2012},
  month = feb,
  volume = {6},
  pages = {320--329},
  publisher = {{Nature Publishing Group}},
  issn = {1751-7370},
  doi = {10.1038/ismej.2011.109},
  abstract = {Despite a long-suspected role in the development of human colorectal cancer (CRC), the composition of gut microbiota in CRC patients has not been adequately described. In this study, fecal bacterial diversity in CRC patients (n=46) and healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 region of the 16S ribosomal RNA gene. Both principal component analysis and UniFrac analysis showed structural segregation between the two populations. Forty-eight operational taxonomic units (OTUs) were identified by redundancy analysis as key variables significantly associated with the structural difference. One OTU closely related to Bacteroides fragilis was enriched in the gut microbiota of CRC patients, whereas three OTUs related to Bacteroides vulgatus and Bacteroides uniformis were enriched in that of healthy volunteers. A total of 11 OTUs belonging to the genera Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus and Peptostreptococcus were significantly more abundant in the gut microbiota of CRC patients, and 5 OTUs belonging to the genus Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae were less abundant. Real-time quantitative PCR further validated the significant reduction of butyrate-producing bacteria in the gut microbiota of CRC patients by measuring the copy numbers of butyryl-coenzyme A CoA transferase genes (Mann\textendash Whitney test, P{$<$}0.01). Reduction of butyrate producers and increase of opportunistic pathogens may constitute a major structural imbalance of gut microbiota in CRC patients.},
  copyright = {2012 International Society for Microbial Ecology},
  journal = {The ISME Journal},
  language = {en},
  number = {2}
}

@article{warrierTMAOGeneratingEnzymeFlavin2015,
  title = {The {{TMAO}}-{{Generating Enzyme Flavin Monooxygenase}} 3 {{Is}} a {{Central Regulator}} of {{Cholesterol Balance}}},
  author = {Warrier, Manya and Shih, Diana M. and Burrows, Amy C. and Ferguson, Daniel and Gromovsky, Anthony D. and Brown, Amanda L. and Marshall, Stephanie and McDaniel, Allison and Schugar, Rebecca C. and Wang, Zeneng and Sacks, Jessica and Rong, Xin and Vallim, Thomas de Aguiar and Chou, Jeff and Ivanova, Pavlina T. and Myers, David S. and Brown, H. Alex and Lee, Richard G. and Crooke, Rosanne M. and Graham, Mark J. and Liu, Xiuli and Parini, Paolo and Tontonoz, Peter and Lusis, Aldon J. and Hazen, Stanley L. and Temel, Ryan E. and Brown, J. Mark},
  year = {2015},
  month = jan,
  volume = {10},
  pages = {326--338},
  publisher = {{Elsevier}},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2014.12.036},
  abstract = {{$<$}h2{$>$}Summary{$<$}/h2{$><$}p{$>$}Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.{$<$}/p{$>$}},
  journal = {Cell Reports},
  language = {English},
  number = {3},
  pmid = {25600868}
}

@article{wenInnateImmunityIntestinal2008,
  title = {Innate Immunity and Intestinal Microbiota in the Development of {{Type}} 1 Diabetes},
  author = {Wen, Li and Ley, Ruth E. and Volchkov, Pavel Yu and Stranges, Peter B. and Avanesyan, Lia and Stonebraker, Austin C. and Hu, Changyun and Wong, F. Susan and Szot, Gregory L. and Bluestone, Jeffrey A. and Gordon, Jeffrey I. and Chervonsky, Alexander V.},
  year = {2008},
  month = oct,
  volume = {455},
  pages = {1109--1113},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature07336},
  abstract = {The effect of deficiency of MyD88 on the generation of type 1 diabetes (T1D) has been investigated through the generation of congenic strains in the non-obese diabetic (NOD) mouse model. It is found that in specific pathogen-free conditions, MyD88-deficiency attenuates T1D, indicating that the interaction of intestinal microbes with the innate immune system is a critical factor in modifying susceptibility to type 1 diabetes.},
  copyright = {2008 Macmillan Publishers Limited. All rights reserved},
  journal = {Nature},
  keywords = {粘膜免疫,里程碑},
  language = {en},
  number = {7216}
}

@article{wlodarskaIntegrativeViewMicrobiomeHost2015,
  title = {An {{Integrative View}} of {{Microbiome}}-{{Host Interactions}} in {{Inflammatory Bowel Diseases}}},
  author = {Wlodarska, Marta and Kostic, Aleksandar D. and Xavier, Ramnik J.},
  year = {2015},
  month = may,
  volume = {17},
  pages = {577--591},
  issn = {19313128},
  doi = {10.1016/j.chom.2015.04.008},
  journal = {Cell Host \& Microbe},
  language = {en},
  number = {5}
}

@article{wuGutresidingSegmentedFilamentous2010,
  title = {Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via {{T}} Helper 17 Cells},
  author = {Wu, Hsin-Jung and Ivanov, Ivaylo I. and Darce, Jaime and Hattori, Kimie and Shima, Tatsuichiro and Umesaki, Yoshinori and Littman, Dan R. and Benoist, Christophe and Mathis, Diane},
  year = {2010},
  month = jun,
  volume = {32},
  pages = {815--827},
  issn = {1097-4180},
  doi = {10.1016/j.immuni.2010.06.001},
  abstract = {Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.},
  journal = {Immunity},
  keywords = {粘膜免疫,里程碑},
  language = {eng},
  number = {6},
  pmcid = {PMC2904693},
  pmid = {20620945}
}

@article{wuHumanColonicCommensal2009,
  title = {A Human Colonic Commensal Promotes Colon Tumorigenesis via Activation of {{T}} Helper Type 17 {{T}} Cell Responses},
  author = {Wu, Shaoguang and Rhee, Ki-Jong and Albesiano, Emilia and Rabizadeh, Shervin and Wu, Xinqun and Yen, Hung-Rong and Huso, David L. and Brancati, Frederick L. and Wick, Elizabeth and McAllister, Florencia and Housseau, Franck and Pardoll, Drew M. and Sears, Cynthia L.},
  year = {2009},
  month = sep,
  volume = {15},
  pages = {1016--1022},
  publisher = {{Nature Publishing Group}},
  issn = {1546-170X},
  doi = {10.1038/nm.2015},
  abstract = {Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.},
  copyright = {2009 Nature Publishing Group},
  journal = {Nature Medicine},
  language = {en},
  number = {9}
}

@article{wuLinkingLongtermDietary2011,
  title = {Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes},
  author = {Wu, Gary D. and Chen, Jun and Hoffmann, Christian and Bittinger, Kyle and Chen, Ying-Yu and Keilbaugh, Sue A. and Bewtra, Meenakshi and Knights, Dan and Walters, William A. and Knight, Rob and Sinha, Rohini and Gilroy, Erin and Gupta, Kernika and Baldassano, Robert and Nessel, Lisa and Li, Hongzhe and Bushman, Frederic D. and Lewis, James D.},
  year = {2011},
  month = oct,
  volume = {334},
  pages = {105--108},
  issn = {1095-9203},
  doi = {10.1126/science.1208344},
  abstract = {Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.},
  journal = {Science (New York, N.Y.)},
  keywords = {菌群稳定性,里程碑},
  language = {eng},
  number = {6052},
  pmcid = {PMC3368382},
  pmid = {21885731}
}

@misc{wumengShaLongSuJiWuMengGordonErSanShiYuWoMenDeLiangYanYanJiu,
  title = {沙龙速记 | 吴萌：{{Gordon二三事与我们的惊艳研究}}},
  author = {吴萌},
  abstract = {大名鼎鼎的Jeffrey Gordon，有什么故事？如何精准调控肠道微生物？},
  howpublished = {http://mp.weixin.qq.com/s?\_\_biz=MzUxNjkwNzkzMQ==\&mid=2247486766\&idx=1\&sn=077cd5f9b33e2be5d721e78e58505ec9\&chksm=f9a17bdaced6f2ccaba40372f24906608461d1a33a38661e91f96ee14a4b6e192e6e56efce00\#rd},
  journal = {WeChat Official Accounts Platform}
}

@article{wuMetforminAltersGut2017,
  title = {Metformin Alters the Gut Microbiome of Individuals with Treatment-Naive Type 2 Diabetes, Contributing to the Therapeutic Effects of the Drug},
  author = {Wu, Hao and Esteve, Eduardo and Tremaroli, Valentina and Khan, Muhammad Tanweer and Caesar, Robert and {Manner{\aa}s-Holm}, Louise and St{\aa}hlman, Marcus and Olsson, Lisa M. and Serino, Matteo and {Planas-F{\`e}lix}, Merc{\`e} and Xifra, Gemma and Mercader, Josep M. and Torrents, David and Burcelin, R{\'e}my and Ricart, Wifredo and Perkins, Rosie and {Fern{\`a}ndez-Real}, Jos{\'e} Manuel and B{\"a}ckhed, Fredrik},
  year = {2017},
  month = jul,
  volume = {23},
  pages = {850--858},
  publisher = {{Nature Publishing Group}},
  issn = {1546-170X},
  doi = {10.1038/nm.4345},
  abstract = {A randomized clinical trial reveals that the antidiabetic effects of metformin are at least partially due to beneficial changes in the microbiota.},
  copyright = {2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature Medicine},
  language = {en},
  number = {7}
}

@article{yangIntestinalFungiContribute2017,
  title = {Intestinal Fungi Contribute to Development of Alcoholic Liver Disease},
  author = {Yang, An-Ming and Inamine, Tatsuo and Hochrath, Katrin and Chen, Peng and Wang, Lirui and Llorente, Cristina and Bluemel, Sena and Hartmann, Phillipp and Xu, Jun and Koyama, Yukinori and Kisseleva, Tatiana and Torralba, Manolito G. and Moncera, Kelvin and Beeri, Karen and Chen, Chien-Sheng and Freese, Kim and Hellerbrand, Claus and Lee, Serene Ml and Hoffman, Hal M. and Mehal, Wajahat Z. and {Garcia-Tsao}, Guadalupe and Mutlu, Ece A. and Keshavarzian, Ali and Brown, Gordon D. and Ho, Samuel B. and Bataller, Ramon and St{\"a}rkel, Peter and Fouts, Derrick E. and Schnabl, Bernd},
  year = {2017},
  month = jun,
  volume = {127},
  pages = {2829--2841},
  issn = {1558-8238},
  doi = {10.1172/JCI90562},
  abstract = {Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal {$\beta$}-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased {$\beta$}-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that {$\beta$}-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1{$\beta$} expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.},
  journal = {The Journal of Clinical Investigation},
  keywords = {真菌和病毒,里程碑},
  language = {eng},
  number = {7},
  pmcid = {PMC5490775},
  pmid = {28530644}
}

@article{yangtaoGutDysbiosisLinked2015,
  title = {Gut {{Dysbiosis Is Linked}} to {{Hypertension}}},
  author = {{Yang Tao} and {Santisteban Monica M.} and {Rodriguez Vermali} and {Li Eric} and {Ahmari Niousha} and {Carvajal Jessica Marulanda} and {Zadeh Mojgan} and {Gong Minghao} and {Qi Yanfei} and {Zubcevic Jasenka} and {Sahay Bikash} and {Pepine Carl J.} and {Raizada Mohan K.} and {Mohamadzadeh Mansour}},
  year = {2015},
  month = jun,
  volume = {65},
  pages = {1331--1340},
  publisher = {{American Heart Association}},
  doi = {10.1161/HYPERTENSIONAHA.115.05315},
  abstract = {Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.},
  journal = {Hypertension},
  number = {6}
}

@article{yassourStrainLevelAnalysisMothertoChild2018,
  title = {Strain-{{Level Analysis}} of {{Mother}}-to-{{Child Bacterial Transmission}} during the {{First Few Months}} of {{Life}}},
  author = {Yassour, Moran and Jason, Eeva and Hogstrom, Larson J. and Arthur, Timothy D. and Tripathi, Surya and Siljander, Heli and Selvenius, Jenni and Oikarinen, Sami and Hy{\"o}ty, Heikki and Virtanen, Suvi M. and Ilonen, Jorma and Ferretti, Pamela and Pasolli, Edoardo and Tett, Adrian and Asnicar, Francesco and Segata, Nicola and Vlamakis, Hera and Lander, Eric S. and Huttenhower, Curtis and Knip, Mikael and Xavier, Ramnik J.},
  year = {2018},
  month = nov,
  volume = {24},
  pages = {146-154.e4},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2018.06.007},
  abstract = {Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, sampled longitudinally in the first months of each child's life. We identified mother-to-child bacterial transmission events and describe the incidence of family-specific antibiotic resistance genes. We observed two inheritance patterns across multiple species, where often the mother's dominant strain is transmitted to the child, but occasionally her secondary strains colonize the infant gut. In families where the secondary strain of B.~uniformis was inherited, a starch utilization gene cluster that was absent in the mother's dominant strain was identified in the child, suggesting the selective advantage of a mother's secondary strain in the infant gut. Our findings reveal mother-to-child bacterial transmission events at high resolution and give insights into early colonization of the infant gut.},
  journal = {Cell Host \& Microbe},
  keywords = {菌群发育,里程碑},
  language = {eng},
  number = {1},
  pmcid = {PMC6091882},
  pmid = {30001517}
}

@article{yatsunenkoHumanGutMicrobiome2012,
  title = {Human Gut Microbiome Viewed across Age and Geography},
  author = {Yatsunenko, Tanya and Rey, Federico E. and Manary, Mark J. and Trehan, Indi and {Dominguez-Bello}, Maria Gloria and Contreras, Monica and Magris, Magda and Hidalgo, Glida and Baldassano, Robert N. and Anokhin, Andrey P. and Heath, Andrew C. and Warner, Barbara and Reeder, Jens and Kuczynski, Justin and Caporaso, J. Gregory and Lozupone, Catherine A. and Lauber, Christian and Clemente, Jose Carlos and Knights, Dan and Knight, Rob and Gordon, Jeffrey I.},
  year = {2012},
  month = jun,
  volume = {486},
  pages = {222--227},
  publisher = {{Nature Publishing Group}},
  issn = {1476-4687},
  doi = {10.1038/nature11053},
  abstract = {The human gut microbiome from a large cohort of more than 500 indivduals living on three continents with three distinct cultures is analysed, emphasizing the effect of host age, diet and environment on the composition and functional repertoire of fecal microbiota.},
  copyright = {2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
  journal = {Nature},
  keywords = {菌群发育,里程碑},
  language = {en},
  number = {7402}
}

@article{zhangHumanGutMicrobiota2013,
  title = {Human {{Gut Microbiota Changes Reveal}} the {{Progression}} of {{Glucose Intolerance}}},
  author = {Zhang, Xiuying and Shen, Dongqian and Fang, Zhiwei and Jie, Zhuye and Qiu, Xinmin and Zhang, Chunfang and Chen, Yingli and Ji, Linong},
  year = {2013},
  month = aug,
  volume = {8},
  pages = {e71108},
  publisher = {{Public Library of Science}},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0071108},
  abstract = {To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.},
  journal = {PLOS ONE},
  language = {en},
  number = {8}
}

@article{zhernakovaPopulationbasedMetagenomicsAnalysis2016,
  title = {Population-Based Metagenomics Analysis Reveals Markers for Gut Microbiome Composition and Diversity},
  author = {Zhernakova, A. and Kurilshikov, A. and Bonder, M. J. and Tigchelaar, E. F. and Schirmer, M. and Vatanen, T. and Mujagic, Z. and Vila, A. V. and Falony, G. and {Vieira-Silva}, S. and Wang, J. and Imhann, F. and Brandsma, E. and Jankipersadsing, S. A. and Joossens, M. and Cenit, M. C. and Deelen, P. and Swertz, M. A. and {LifeLines cohort study} and Weersma, R. K. and Feskens, E. J. M. and Netea, M. G. and Gevers, D. and Jonkers, D. and Franke, L. and Aulchenko, Y. S. and Huttenhower, C. and Raes, J. and Hofker, M. H. and Xavier, R. J. and Wijmenga, C. and Fu, J.},
  year = {2016},
  month = apr,
  volume = {352},
  pages = {565--569},
  issn = {0036-8075, 1095-9203},
  doi = {10.1126/science.aad3369},
  journal = {Science},
  language = {en},
  number = {6285}
}

@article{zhuGutMicrobialMetabolite2016,
  title = {Gut {{Microbial Metabolite TMAO Enhances Platelet Hyperreactivity}} and {{Thrombosis Risk}}},
  author = {Zhu, Weifei and Gregory, Jill C. and Org, Elin and Buffa, Jennifer A. and Gupta, Nilaksh and Wang, Zeneng and Li, Lin and Fu, Xiaoming and Wu, Yuping and Mehrabian, Margarete and Sartor, R. Balfour and McIntyre, Thomas M. and Silverstein, Roy L. and Tang, W. H. Wilson and DiDonato, Joseph A. and Brown, J. Mark and Lusis, Aldons J. and Hazen, Stanley L.},
  year = {2016},
  month = mar,
  volume = {165},
  pages = {111--124},
  publisher = {{Elsevier}},
  issn = {0092-8674, 1097-4172},
  doi = {10.1016/j.cell.2016.02.011},
  abstract = {{$<$}h2{$>$}Summary{$<$}/h2{$><$}p{$>$}Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n {$>$} 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca\textsuperscript{2+} release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.{$<$}/p{$>$}},
  journal = {Cell},
  language = {English},
  number = {1},
  pmid = {26972052}
}

@article{zimmermannSeparatingHostMicrobiome2019a,
  title = {Separating Host and Microbiome Contributions to Drug Pharmacokinetics and Toxicity},
  author = {Zimmermann, Michael and {Zimmermann-Kogadeeva}, Maria and Wegmann, Rebekka and Goodman, Andrew L.},
  year = {2019},
  month = aug,
  volume = {363},
  issn = {1095-9203},
  doi = {10.1126/science.aat9931},
  abstract = {The gut microbiota is implicated in the metabolism of many medical drugs, with consequences for interpersonal variation in drug efficacy and toxicity. However, quantifying microbial contributions to drug metabolism is challenging, particularly in cases where host and microbiome perform the same metabolic transformation. We combined gut commensal genetics with gnotobiotics to measure brivudine drug metabolism across tissues in mice that vary in a single microbiome-encoded enzyme. Informed by these measurements, we built a pharmacokinetic model that quantitatively predicts microbiome contributions to systemic drug and metabolite exposure, as a function of bioavailability, host and microbial drug-metabolizing activity, drug and metabolite absorption, and intestinal transit kinetics. Clonazepam studies illustrate how this approach disentangles microbiome contributions to metabolism of drugs subject to multiple metabolic routes and transformations.},
  journal = {Science (New York, N.Y.)},
  keywords = {药物代谢,里程碑},
  language = {eng},
  number = {6427},
  pmcid = {PMC6533120},
  pmid = {30733391}
}

@article{zmoraTakingItPersonally2016a,
  ids = {zmoraTakingItPersonally2016},
  title = {Taking It {{Personally}}: {{Personalized Utilization}} of the {{Human Microbiome}} in {{Health}} and {{Disease}}},
  shorttitle = {Taking It {{Personally}}},
  author = {Zmora, Niv and Zeevi, David and Korem, Tal and Segal, Eran and Elinav, Eran},
  year = {2016},
  month = jan,
  volume = {19},
  pages = {12--20},
  issn = {1934-6069},
  doi = {10.1016/j.chom.2015.12.016},
  abstract = {The genomic revolution enabled the clinical inclusion of an immense body of person-specific information to an extent that is revolutionizing medicine and science. The gut microbiome, our "second genome," dynamically integrates signals from the host and its environment, impacting health and risk of disease. Herein, we summarize how individualized characterization of the microbiome composition and function may assist in personalized diagnostic assessment, risk stratification, disease prevention, treatment decision-making, and patients' follow up. We further discuss the limitations, pitfalls, and challenges that the microbiome field faces in integrating patient-specific microbial data into the clinical realm. Finally, we highlight how recent insights into personalized modulation of the microbiome, by nutritional and pre-, pro-, and post-biotic intervention, may lead to development of individualized approaches that may enable us to harness the microbiome as a central precision medicine target.},
  journal = {Cell Host \& Microbe},
  keywords = {Bacteria,Gastrointestinal Microbiome,Gastrointestinal Tract,Humans,Precision Medicine},
  language = {eng},
  number = {1},
  pmid = {26764593}
}