The human microbiome: from symbiosis to pathogenesis.

The human microbiota is a complex assemblage of the microbes inhabiting many sites in the human body. Recent advances in technology have enabled deep sequencing and analysis of the members and structures of these communities. Two sites, the vagina and gastrointestinal tract, are highlighted to exemplify how technological advances have enhanced our knowledge of the host-microbiota system. These examples represent low- and high-complexity communities, respectively. In each example, certain community structures are identified that can be extrapolated to larger collections representing multiple individuals and potential disease or health states. One common feature is the unexpected diversity of the microbiota at any of these locations, which poses a challenge for relating the microbiota to health and disease. However, we anticipate microbiota compositional measurements could become standard clinical practice in the future and may become diagnostic for certain diseases or increased susceptibility to certain disorders. The microbiota of a number of disease states are currently being examined to identify potential correlations. In line with these predictions, it is possible that existing conditions may be resolved by altering the microbiota in a positive way.

[1]  R. Knight,et al.  Moving pictures of the human microbiome , 2011, Genome Biology.

[2]  S. Dusko Ehrlich,et al.  MetaHIT: The European Union Project on Metagenomics of the Human Intestinal Tract , 2011 .

[3]  J. Gordon,et al.  Human nutrition, the gut microbiome and the immune system , 2011, Nature.

[4]  P. Gajer,et al.  Vaginal microbiome of reproductive-age women , 2010, Proceedings of the National Academy of Sciences.

[5]  P. Matzinger The Danger Model: A Renewed Sense of Self , 2002, Science.

[6]  N. Pace,et al.  Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases , 2007, Proceedings of the National Academy of Sciences.

[7]  S. Tringe,et al.  Metagenomic Discovery of Biomass-Degrading Genes and Genomes from Cow Rumen , 2011, Science.

[8]  J. Doré,et al.  Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients , 2008, Proceedings of the National Academy of Sciences.

[9]  J. Clemente,et al.  Human gut microbiome viewed across age and geography , 2012, Nature.

[10]  W. M. Vos,et al.  Microbes inside—from diversity to function: the case of Akkermansia , 2012, The ISME Journal.

[11]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[12]  C. Johnson,et al.  Linking richness, community variability, and invasion resistance with patch size. , 2006, Ecology.

[13]  L. Meyn,et al.  Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  Michael Roth,et al.  Targeting QseC Signaling and Virulence for Antibiotic Development , 2008, Science.

[15]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

[16]  Vanessa Sperandio,et al.  Inter-kingdom signaling: chemical language between bacteria and host. , 2009, Current opinion in microbiology.

[17]  P. Turnbaugh,et al.  The core gut microbiome, energy balance and obesity , 2009, The Journal of physiology.

[18]  D. Relman,et al.  Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation , 2010, Proceedings of the National Academy of Sciences.

[19]  Zaid Abdo,et al.  Temporal Dynamics of the Human Vaginal Microbiota , 2012, Science Translational Medicine.

[20]  William A. Walters,et al.  Experimental and analytical tools for studying the human microbiome , 2011, Nature Reviews Genetics.

[21]  A. Gieseke,et al.  Real-Time Microsensor Measurement of Local Metabolic Activities in Ex Vivo Dental Biofilms Exposed to Sucrose and Treated with Chlorhexidine , 2010, Applied and Environmental Microbiology.

[22]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[23]  B. Chohan,et al.  Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. , 1999, The Journal of infectious diseases.

[24]  Rob Knight,et al.  Bayesian community-wide culture-independent microbial source tracking , 2011, Nature Methods.

[25]  F. Bushman,et al.  Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes , 2011, Science.

[26]  E. Bosmans,et al.  Pathogenesis of abnormal vaginal bacterial flora. , 2000, American journal of obstetrics and gynecology.

[27]  J. Marrazzo,et al.  Molecular identification of bacteria associated with bacterial vaginosis. , 2005, The New England journal of medicine.

[28]  Michael Mitzenmacher,et al.  Detecting Novel Associations in Large Data Sets , 2011, Science.

[29]  B. Birren,et al.  Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. , 2012, Genome research.

[30]  J. Goedert,et al.  Assessment of the human faecal microbiota: II. Reproducibility and associations of 16S rRNA pyrosequences , 2012, European journal of clinical investigation.

[31]  J. Roth,et al.  Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota , 2011, Proceedings of the National Academy of Sciences.

[32]  S. Sørensen,et al.  Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults , 2010, PloS one.

[33]  R. Knight,et al.  Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns , 2010, Proceedings of the National Academy of Sciences.

[34]  Vanessa Sperandio,et al.  Bacteria–host communication: The language of hormones , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Gordon,et al.  A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  H. Khamis,et al.  Distal gut microbiota of adolescent children is different from that of adults. , 2011, FEMS microbiology ecology.

[37]  Belgin Dogan,et al.  Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota , 2012, Science.

[38]  Lu Wang,et al.  The NIH Human Microbiome Project. , 2009, Genome research.

[39]  Vanessa Sperandio,et al.  Inter-kingdom signalling: communication between bacteria and their hosts , 2008, Nature Reviews Microbiology.

[40]  A. Chervonsky,et al.  Successful Transmission of a Retrovirus Depends on the Commensal Microbiota , 2011, Science.

[41]  Vernon Ahmadjian,et al.  Symbiosis: An Introduction to Biological Associations , 1988 .

[42]  S. Hillier,et al.  Control of the microbial flora of the vagina by H2O2-generating lactobacilli. , 1991, The Journal of infectious diseases.

[43]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[44]  Min Zhang,et al.  Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors , 2010, Proceedings of the National Academy of Sciences.

[45]  R. Knight,et al.  The Human Microbiome Project , 2007, Nature.

[46]  Olli Simell,et al.  Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes , 2011, PloS one.

[47]  Sharon I. Greenblum,et al.  Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease , 2011, Proceedings of the National Academy of Sciences.

[48]  K. Peeyananjarassri,et al.  Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogens. , 2006, FEMS immunology and medical microbiology.

[49]  Maria Karlsson,et al.  Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. , 2010, Cell host & microbe.

[50]  S. Giovannoni,et al.  The uncultured microbial majority. , 2003, Annual review of microbiology.

[51]  F. Shanahan,et al.  The gut flora as a forgotten organ , 2006, EMBO reports.

[52]  V. Sperandio,et al.  Anti-virulence strategies to combat bacteria-mediated disease , 2010, Nature Reviews Drug Discovery.

[53]  Jose U. Scher,et al.  The microbiome and rheumatoid arthritis , 2011, Nature Reviews Rheumatology.

[54]  K. Whaley,et al.  Acid Production by Vaginal Flora In Vitro Is Consistent with the Rate and Extent of Vaginal Acidification , 1999, Infection and Immunity.

[55]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[56]  Jonathan Krakoff,et al.  Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. , 2011, The American journal of clinical nutrition.

[57]  K. Whaley,et al.  Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. , 2001, Human reproduction.

[58]  Wolf-Dietrich Hardt,et al.  Mechanisms controlling pathogen colonization of the gut. , 2011, Current opinion in microbiology.

[59]  Vanessa Sperandio,et al.  Bacterial Cell-to-Cell Signaling in the Gastrointestinal Tract , 2005, Infection and Immunity.

[60]  P. Gajer,et al.  Proof of Concept of Microbiome-Metabolome Analysis and Delayed Gluten Exposure on Celiac Disease Autoimmunity in Genetically At-Risk Infants , 2012, PloS one.

[61]  Rob Knight,et al.  Our microbial selves: what ecology can teach us , 2011, EMBO reports.

[62]  Richard A. Moore,et al.  Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. , 2012, Genome research.

[63]  J. Roth,et al.  Gut inflammation provides a respiratory electron acceptor for Salmonella , 2010, Nature.

[64]  F. Bushman,et al.  The human gut virome: inter-individual variation and dynamic response to diet. , 2011, Genome research.

[65]  E. Mardis,et al.  An obesity-associated gut microbiome with increased capacity for energy harvest , 2006, Nature.

[66]  P. Diaz Microbial diversity and interactions in subgingival biofilm communities. , 2012, Frontiers of oral biology.

[67]  C. Deming,et al.  Topographical and Temporal Diversity of the Human Skin Microbiome , 2009, Science.

[68]  J. A. Aas,et al.  Defining the Normal Bacterial Flora of the Oral Cavity , 2005, Journal of Clinical Microbiology.

[69]  Jennifer C. Drew,et al.  Toward defining the autoimmune microbiome for type 1 diabetes , 2011, The ISME Journal.

[70]  Jeanne M. Marrazzo,et al.  Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria , 2012, PloS one.

[71]  E. Greenberg,et al.  Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. , 2001, Annual review of genetics.

[72]  L. T. Angenent,et al.  Succession of microbial consortia in the developing infant gut microbiome , 2010, Proceedings of the National Academy of Sciences.

[73]  D. Kasper,et al.  A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease , 2010, Mucosal Immunology.

[74]  J. Sobel Is there a protective role for vaginal flora? , 1999, Current infectious disease reports.

[75]  Andrea J Pruijssers,et al.  Intestinal Microbiota Promote Enteric Virus Replication and Systemic Pathogenesis , 2011, Science.

[76]  E. Rubin,et al.  Chemical biology and bacteria: not simply a matter of life or death. , 2006, Current opinion in chemical biology.

[77]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[78]  B. Leggett,et al.  Numerical ecology validates a biogeographical distribution and gender-based effect on mucosa-associated bacteria along the human colon , 2011, The ISME Journal.

[79]  E. Greenberg,et al.  Self perception in bacteria: quorum sensing with acylated homoserine lactones. , 1998, Current opinion in microbiology.

[80]  J. Mekalanos,et al.  Small-Molecule Inhibitor of Vibrio cholerae Virulence and Intestinal Colonization , 2005, Science.

[81]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[82]  P. Brigidi,et al.  Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians , 2010, PloS one.

[83]  G. Huffnagle,et al.  The "Microflora Hypothesis" of allergic disease. , 2008, Advances in experimental medicine and biology.

[84]  J. Doré,et al.  Differences in Fecal Microbiota in Different European Study Populations in Relation to Age, Gender, and Country: a Cross-Sectional Study , 2006, Applied and Environmental Microbiology.

[85]  J. Palefsky,et al.  Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women. , 2005, The Journal of infectious diseases.

[86]  James H. Bullard,et al.  Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. , 2011, The New England journal of medicine.

[87]  Katherine H. Huang,et al.  A framework for human microbiome research , 2012, Nature.

[88]  R. Ley,et al.  The Antibacterial Lectin RegIIIγ Promotes the Spatial Segregation of Microbiota and Host in the Intestine , 2011, Science.

[89]  P. Bork,et al.  Enterotypes of the human gut microbiome , 2011, Nature.

[90]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.