Structure, function and diversity of the healthy human microbiome

Journal name:
Nature
Volume:
486,
Pages:
207–214
Date published:
DOI:
doi:10.1038/nature11234
Received
Accepted
Published online

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 81–99% 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.

At a glance

Figures

  1. Diversity of the human microbiome is concordant among measures, unique to each individual, and strongly determined by microbial habitat.
    Figure 1: Diversity of the human microbiome is concordant among measures, unique to each individual, and strongly determined by microbial habitat.

    a, Alpha diversity within subjects by body habitat, grouped by area, as measured using the relative inverse Simpson index of genus-level phylotypes (cyan), 16S rRNA gene OTUs (blue), shotgun metagenomic reads matched to reference genomes (orange), functional modules (dark orange), and enzyme families (yellow). The mouth generally shows high within-subject diversity and the vagina low diversity, with other habitats intermediate; variation among individuals often exceeds variation among body habitats. b, Bray–Curtis beta diversity among subjects by body habitat, colours as for a. Skin differs most between subjects, with oral habitats and vaginal genera more stable. Although alpha- and beta-diversity are not directly comparable, changes in structure among communities (a) occupy a wider dynamic range than do changes within communities among individuals (b). c, Principal coordinates plot showing variation among samples demonstrates that primary clustering is by body area, with the oral, gastrointestinal, skin and urogenital habitats separate; the nares habitat bridges oral and skin habitats. d, Repeated samples from the same subject (blue) are more similar than microbiomes from different subjects (red). Technical replicates (grey) are in turn more similar; these patterns are consistent for all body habitats and for both phylogenetic and metabolic community composition. See previously described sample counts1 for all comparisons.

  2. Carriage of microbial taxa varies while metabolic pathways remain stable within a healthy population.
    Figure 2: Carriage of microbial taxa varies while metabolic pathways remain stable within a healthy population.

    a, b, Vertical bars represent microbiome samples by body habitat in the seven locations with both shotgun and 16S data; bars indicate relative abundances colored by microbial phyla from binned OTUs (a) and metabolic modules (b). Legend indicates most abundant phyla/pathways by average within one or more body habitats; RC, retroauricular crease. A plurality of most communities’ memberships consists of a single dominant phylum (and often genus; see Supplementary Fig. 2), but this is universal neither to all body habitats nor to all individuals. Conversely, most metabolic pathways are evenly distributed and prevalent across both individuals and body habitats.

  3. Abundant taxa in the human microbiome that have been metagenomically and taxonomically well defined in the HMP population.
    Figure 3: Abundant taxa in the human microbiome that have been metagenomically and taxonomically well defined in the HMP population.

    ac, Prevalence (intensity, colour denoting phylum/class) and abundance when present (size) of clades in the healthy microbiome. The most abundant metagenomically-identified species (a), 16S-identified genera (b) and PATRIC12 pathogens (metagenomic) (c) are shown. d, e, The population size and sequencing depths of the HMP have well defined the microbiome at all assayed body sites, as assessed by saturation of added community metabolic configurations (rarefaction of minimum Bray–Curtis beta-diversity of metagenomic enzyme class abundances to nearest neighbour, inter-quartile range over 100 samples) (d) and phylogenetic configurations (minimum 16S OTU weighted UniFrac distance to nearest neighbour) (e).

  4. Microbial carriage varies between subjects down to the species and strain level.
    Figure 4: Microbial carriage varies between subjects down to the species and strain level.

    Metagenomic reads from 127 tongue samples spanning 90 subjects were processed with MetaPhlAn to determine relative abundances for each species. a, Relative abundances of 11 distinct Streptococcus spp. In addition to variation in broader clades (see Fig. 2), individual species within a single habitat demonstrate a wide range of compositional variation. Inset illustrates average tongue sample composition. b, Metabolic modules present/absent (grey/white) in KEGG24 reference genomes of tongue streptococci denote selected areas of strain-specific functional differentiation. cpnt, component. c, Comparative genomic coverage for the single Streptococcus mitis B6 strain. Grey dots are median reads per kilobase per million reads (RPKM) for 1-kb windows, grey bars are the 25th to 75th percentiles across all samples, red line the LOWESS-smoothed average. Red bars at the bottom highlight predicted genomic islands27. Large, discrete, and highly variable islands are commonly under-represented. d, Two islands are highlighted, V (V-type H+ ATPase subunits I, K, E, C, F, A and B) and CH (choline-binding proteins cbp6 and cbp12), indicating functional cohesion of strain-specific gene loss within individual human hosts.

  5. Microbial community membership and function correlates with host phenotype and sample metadata.
    Figure 5: Microbial community membership and function correlates with host phenotype and sample metadata.

    ad, The pathway and clade abundances most significantly associated (all FDR q<0.2) using a multivariate linear model with subject race or ethnicity (a), vaginal posterior fornix pH (b), subject age (c) and BMI (d). Scatter plots of samples are shown with lines indicating best simple linear fit. Race/ethnicity and vaginal pH are particularly strong associations; age and BMI are more representative of typically modest phenotypic associations (Supplementary Table 3), suggesting that variation in the healthy microbiota may correspond to other host or environmental factors.

References

  1. The Human Microbiome Project Consortium. A framework for human microbiome research. Nature http://dx.doi.org/10.1038/nature11209 (this issue)
  2. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480484 (2009)
  3. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 5965 (2010)
  4. Fredricks, D. N., Fiedler, T. L. & Marrazzo, J. M. Molecular identification of bacteria associated with bacterial vaginosis. N. Engl. J. Med. 353, 18991911 (2005)
  5. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 16941697 (2009)
  6. Huse, S., Ye, Y., Zhou, Y. & Fodor, A. A core human microbiome as viewed through 16s rRNA sequences clusters. PLoS ONE http://dx.doi.org/10.1371/journal.pone.0034242 (14 June 2012)
  7. Li, K., Bihan, M., Yooseph, S. & Methe, B. A. Analyses of the microbial diversity across the human microbiome. PLoS ONE http://dx.doi.org/10.1371/journal.pone.0032118 (14 June 2012)
  8. Grice, E. A. et al. Topographical and temporal diversity of the human skin microbiome. Science 324, 11901192 (2009)
  9. Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl Acad. Sci. USA 108 (Suppl 1). 46804687 (2011)
  10. Segata, N. et al. Composition of the adult digestive tract microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 13, R42 (2012)
  11. Segata, N. et al. Efficient metagenomic microbial community profiling using unique clade-specific marker genes. Nature Methods http://dx.doi.org/10.1038/nmeth.2066 (2012)
  12. Gillespie, J. J. et al. PATRIC: the comprehensive bacterial bioinformatics resource with a focus on human pathogenic species. Infect. Immun. 79, 42864298 (2011)
  13. Sharpton, T. J. et al. PhylOTU: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data. PLoS Comput. Biol. 7, e1001061 (2011)
  14. Wylie, K. M. et al. Novel bacterial taxa in the human microbiome. PLoS ONE http://dx.doi.org/10.1371/journal.pone.003529 (14 June 2012)
  15. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 1673116736 (2008)
  16. Aas, J. A., Paster, B. J., Stokes, L. N., Olsen, I. & Dewhirst, F. E. Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol. 43, 57215732 (2005)
  17. Medini, D. et al. Microbiology in the post-genomic era. Nature Rev. Microbiol. 6, 419430 (2008)
  18. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620625 (2008)
  19. Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279289 (2009)
  20. Kuehnert, M. J. et al. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001–2002. J. Infect. Dis. 193, 172179 (2006)
  21. Faust, K. et al. Microbial co-occurrence relationships in the human microbiome. PLoS Comput. Biol. (in the press)
  22. Abubucker, S. et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol. http://dx.doi.org/10.1371/journal.pcbi.1002358 (14 June 2012)
  23. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nature Methods 7, 335336 (2010)
  24. Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M. & Hirakawa, M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38, D355D360 (2010)
  25. Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 26, 589595 (2010)
  26. Giannoukos, G. et al. Efficient and robust RNA-seq process for cultured bacteria and complex community transcriptomes. Genome Biol. 13, R23 (2012)
  27. Langille, M. G. & Brinkman, F. S. IslandViewer: an integrated interface for computational identification and visualization of genomic islands. Bioinformatics 25, 664665 (2009)

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Author information

  1. These authors contributed equally to this work.

    • Curtis Huttenhower &
    • Dirk Gevers

Affiliations

  1. Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

    • Curtis Huttenhower,
    • J. Fah Sathirapongsasuti &
    • Nicola Segata
  2. The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

    • Curtis Huttenhower,
    • Dirk Gevers,
    • Ashlee M. Earl,
    • Michael G. FitzGerald,
    • Sarah K. Young,
    • Qiandong Zeng,
    • Eric J. Alm,
    • Lucia Alvarado,
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    • Toby Bloom,
    • Dawn M. Ciulla,
    • Rachel L. Erlich,
    • Michael Feldgarden,
    • Sheila Fisher,
    • Dennis C. Friedrich,
    • Georgia Giannoukos,
    • Jonathan M. Goldberg,
    • Allison Griggs,
    • Sharvari Gujja,
    • Brian J. Haas,
    • Theresa A. Hepburn,
    • Clinton Howarth,
    • Katherine H. Huang,
    • Cristyn Kells,
    • Niall Lennon,
    • Teena Mehta,
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    • Sean M. Sykes,
    • Diana G. Tabbaa,
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    • Chandri Yandava,
    • Jeremy D. Zucker &
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  3. Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.

    • Rob Knight,
    • Jose C. Clemente,
    • Catherine A. Lozupone &
    • Daniel McDonald
  4. Howard Hughes Medical Institute, Boulder, Colorado 80309, USA.

    • Rob Knight
  5. The Genome Institute, Washington University School of Medicine, St. Louis, Missouri 63108, USA.

    • Sahar Abubucker,
    • Asif T. Chinwalla,
    • Robert S. Fulton,
    • Kymberlie Hallsworth-Pepin,
    • Elizabeth A. Lobos,
    • Vincent Magrini,
    • John C. Martin,
    • Makedonka Mitreva,
    • Erica J. Sodergren,
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    • Elizabeth Appelbaum,
    • Veena Bhonagiri,
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    • Todd Wylie,
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    • Yanjiao Zhou,
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    • Richard K. Wilson
  6. J. Craig Venter Institute, Rockville, Maryland 20850, USA.

    • Jonathan H. Badger,
    • Ramana Madupu,
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  7. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

    • Heather H. Creasy,
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    • Donna M. Muzny,
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  9. Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.

    • James Versalovic
  10. Department of Pathology, Texas Children’s Hospital, Houston, Texas 77030, USA.

    • James Versalovic
  11. Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

    • Kjersti M. Aagaard
  12. Molecular and Cellular Biology, University of Guelph, Guleph, Ontario N1G 2W1, Canada.

    • Emma Allen-Vercoe
  13. Department of Civil & Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

    • Eric J. Alm
  14. Center for Environmental Biotechnology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

    • Gary L. Andersen
  15. School of Dentistry, University of California, San Francisco, San Francisco, California 94143, USA.

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  16. Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.

    • Tulin Ayvaz,
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  17. National Institute of Arthritis and Musculoskeletal and Skin, National Institutes of Health, Bethesda, Maryland 20892, USA.

    • Carl C. Baker
  18. Office of Research on Women’s Health, National Institutes of Health, Bethesda, Maryland 20892, USA.

    • Lisa Begg
  19. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

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  20. Department of Medicine, New York University Langone Medical Center, New York, New York 10016, USA.

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    • Vivien Bonazzi,
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  22. Department of Statistical Sciences and Operations Research, Virginia Commonwealth University, Richmond, Virginia 23284, USA.

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  23. Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia 23284, USA.

    • J. Paul Brooks,
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  24. Department of Biology, Virginia Commonwealth University, Richmond, Virginia 23284, USA.

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  27. Joint Genome Institute, Walnut Creek, California 94598, USA.

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  30. FemCare Product Safety and Regulatory Affairs, The Procter & Gamble Company, Cincinnati, Ohio 45224, USA.

    • Catherine C. Davis
  31. Bioinformatics Department, Second Genome, Inc., San Bruno, California 94066, USA.

    • Todd Z. DeSantis
  32. Department of Molecular Genetics, Forsyth Institute, Cambridge, Massachusetts 02142, USA.

    • Floyd E. Dewhirst,
    • Jacques Izard &
    • Katherine P. Lemon
  33. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.

    • Floyd E. Dewhirst &
    • Jacques Izard
  34. Department of Medicine, Division of General Medical Science, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    • Elena Deych,
    • Patricio S. La Rosa &
    • William D. Shannon
  35. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    • Wm Michael Dunne &
    • Mark A. Watson
  36. bioMerieux, Inc., Durham, South Carolina 27712, USA.

    • Wm Michael Dunne
  37. drive5.com, Tiburon, California 94920, USA.

    • Robert C. Edgar
  38. Center for Ethics, Humanities and Spiritual Care, Cleveland Clinic, Cleveland, Ohio 44195, USA.

    • Ruth M. Farrell &
    • Richard R. Sharp
  39. Department of Structural Biology, VIB, Belgium, 1050 Ixelles, Belgium.

    • Karoline Faust &
    • Jeroen Raes
  40. Department of Applied Biological Sciences (DBIT), Vrije Universiteit Brussel, 1050 Ixelles, Belgium.

    • Karoline Faust &
    • Jeroen Raes
  41. Department of Bioinformatics and Genomics, University of North Carolina - Charlotte, Charlotte, North Carolina 28223, USA.

    • Anthony A. Fodor
  42. Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844, USA.

    • Larry J. Forney
  43. Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

    • Jonathan Friedman &
    • Christopher S. Smillie
  44. Center for Advanced Dental Education, Saint Louis University, St. Louis, Missouri 63104, USA.

    • Nathalia Garcia
  45. Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA.

    • Antonio Gonzalez &
    • Dan Knights
  46. Division of Associated Clinical Specialties and Dental Research Institute, UCLA School of Dentistry, Los Angeles, California 90095, USA.

    • Susan Kinder Haake
  47. University of Maryland Francis King Carey School of Law, Baltimore, Maryland 21201, USA.

    • Diane E. Hoffmann
  48. Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA.

    • Susan M. Huse
  49. Ecology Department, Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

    • Janet K. Jansson
  50. Department of Periodontics, University of Texas Health Science Center School of Dentistry, Houston, Texas 77030, USA.

    • James A. Katancik
  51. Department of Biology, San Diego State University, San Diego, California 92182, USA.

    • Scott T. Kelley &
    • Beltran Rodriguez-Mueller
  52. Faculty of Medicine, McGill University, 3647 Peel St, Montreal, Ouebec H3A 1X1, Canada.

    • Nicholas B. King
  53. Dermatology Branch, CCR, National Cancer Institute, Bethesda, Maryland 20892, USA.

    • Heidi H. Kong
  54. Department of Microbiology, Cornell University, Ithaca, New York 14853, USA.

    • Omry Koren &
    • Ruth E. Ley
  55. Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland 20742, USA.

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  56. Division of Infectious Diseases, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Katherine P. Lemon
  57. Department of Anthropology, University of Oklahoma, Norman, Oklahoma 73019, USA.

    • Cecil M. Lewis &
    • Paul Spicer
  58. Department of Obstetrics and Gynecology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.

    • Tessa Madden
  59. Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

    • Peter J. Mannon
  60. Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas 77030, USA.

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  61. Medicine-Infectious Disease, Baylor College of Medicine, Houston, Texas 77030, USA.

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  62. Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.

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  63. Gladstone Institutes, University of California, San Francisco, San Francisco, California 94158, USA.

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  64. Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94158, USA.

    • Katherine S. Pollard
  65. Division of Biostatistics, University of California, San Francisco, San Francisco, California 94158, USA.

    • Katherine S. Pollard
  66. Department of Computer Science, University of Maryland, College Park, Maryland 20742, USA.

    • Mihai Pop
  67. School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA.

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    • Yuzhen Ye
  68. Mount Sinai School of Medicine, New York, New York 10029, USA.

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  69. Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

    • Kevin P. Riehle
  70. Center for Bioethics and Department of Medical Ethics, University of Pennsylvania, Philadelphia, Pennsylviana 19104, USA.

    • Pamela Sankar
  71. Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.

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  72. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA.

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  73. The EMMES Corporation, Rockville, Maryland 20850, USA.

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  74. Harper University Hospital, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

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  75. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    • Todd J. Treangen
  76. J. Craig Venter Institute, San Diego, California 92121, USA.

    • Shibu Yooseph
  77. Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

    • Laurie Zoloth
  78. Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas 77030, USA.

    • Joseph F. Petrosino
  79. Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.

    • Sean Conlan &
    • Julia A. Segre

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  1. The Human Microbiome Project Consortium

    • Curtis Huttenhower,
    • Dirk Gevers,
    • Rob Knight,
    • Sahar Abubucker,
    • Jonathan H. Badger,
    • Asif T. Chinwalla,
    • Heather H. Creasy,
    • Ashlee M. Earl,
    • Michael G. FitzGerald,
    • Robert S. Fulton,
    • Michelle G. Giglio,
    • Kymberlie Hallsworth-Pepin,
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    • Makedonka Mitreva,
    • Donna M. Muzny,
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    • James Versalovic,
    • Aye M. Wollam,
    • Kim C. Worley,
    • Jennifer R. Wortman,
    • Sarah K. Young,
    • Qiandong Zeng,
    • Kjersti M. Aagaard,
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    • Emma Allen-Vercoe,
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    • Joseph L. Campbell,
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    • Brandi L. Cantarel,
    • Patrick S. G. Chain,
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    • Lei Chen,
    • Shaila Chhibba,
    • Ken Chu,
    • Dawn M. Ciulla,
    • Jose C. Clemente,
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    • Sean Conlan,
    • Jonathan Crabtree,
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    • Todd Z. DeSantis,
    • Carolyn Deal,
    • Kimberley D. Delehaunty,
    • Floyd E. Dewhirst,
    • Elena Deych,
    • Yan Ding,
    • David J. Dooling,
    • Shannon P. Dugan,
    • Wm Michael Dunne,
    • A. Scott Durkin,
    • Robert C. Edgar,
    • Rachel L. Erlich,
    • Candace N. Farmer,
    • Ruth M. Farrell,
    • Karoline Faust,
    • Michael Feldgarden,
    • Victor M. Felix,
    • Sheila Fisher,
    • Anthony A. Fodor,
    • Larry J. Forney,
    • Leslie Foster,
    • Valentina Di Francesco,
    • Jonathan Friedman,
    • Dennis C. Friedrich,
    • Catrina C. Fronick,
    • Lucinda L. Fulton,
    • Hongyu Gao,
    • Nathalia Garcia,
    • Georgia Giannoukos,
    • Christina Giblin,
    • Maria Y. Giovanni,
    • Jonathan M. Goldberg,
    • Johannes Goll,
    • Antonio Gonzalez,
    • Allison Griggs,
    • Sharvari Gujja,
    • Susan Kinder Haake,
    • Brian J. Haas,
    • Holli A. Hamilton,
    • Emily L. Harris,
    • Theresa A. Hepburn,
    • Brandi Herter,
    • Diane E. Hoffmann,
    • Michael E. Holder,
    • Clinton Howarth,
    • Katherine H. Huang,
    • Susan M. Huse,
    • Jacques Izard,
    • Janet K. Jansson,
    • Huaiyang Jiang,
    • Catherine Jordan,
    • Vandita Joshi,
    • James A. Katancik,
    • Wendy A. Keitel,
    • Scott T. Kelley,
    • Cristyn Kells,
    • Nicholas B. King,
    • Dan Knights,
    • Heidi H. Kong,
    • Omry Koren,
    • Sergey Koren,
    • Karthik C. Kota,
    • Christie L. Kovar,
    • Nikos C. Kyrpides,
    • Patricio S. La Rosa,
    • Sandra L. Lee,
    • Katherine P. Lemon,
    • Niall Lennon,
    • Cecil M. Lewis,
    • Lora Lewis,
    • Ruth E. Ley,
    • Kelvin Li,
    • Konstantinos Liolios,
    • Bo Liu,
    • Yue Liu,
    • Chien-Chi Lo,
    • Catherine A. Lozupone,
    • R. Dwayne Lunsford,
    • Tessa Madden,
    • Anup A. Mahurkar,
    • Peter J. Mannon,
    • Elaine R. Mardis,
    • Victor M. Markowitz,
    • Konstantinos Mavromatis,
    • Jamison M. McCorrison,
    • Daniel McDonald,
    • Jean McEwen,
    • Amy L. McGuire,
    • Pamela McInnes,
    • Teena Mehta,
    • Kathie A. Mihindukulasuriya,
    • Jason R. Miller,
    • Patrick J. Minx,
    • Irene Newsham,
    • Chad Nusbaum,
    • Michelle O’Laughlin,
    • Joshua Orvis,
    • Ioanna Pagani,
    • Krishna Palaniappan,
    • Shital M. Patel,
    • Matthew Pearson,
    • Jane Peterson,
    • Mircea Podar,
    • Craig Pohl,
    • Katherine S. Pollard,
    • Mihai Pop,
    • Margaret E. Priest,
    • Lita M. Proctor,
    • Xiang Qin,
    • Jeroen Raes,
    • Jacques Ravel,
    • Jeffrey G. Reid,
    • Mina Rho,
    • Rosamond Rhodes,
    • Kevin P. Riehle,
    • Maria C. Rivera,
    • Beltran Rodriguez-Mueller,
    • Yu-Hui Rogers,
    • Matthew C. Ross,
    • Carsten Russ,
    • Ravi K. Sanka,
    • Pamela Sankar,
    • J. Fah Sathirapongsasuti,
    • Jeffery A. Schloss,
    • Patrick D. Schloss,
    • Thomas M. Schmidt,
    • Matthew Scholz,
    • Lynn Schriml,
    • Alyxandria M. Schubert,
    • Nicola Segata,
    • Julia A. Segre,
    • William D. Shannon,
    • Richard R. Sharp,
    • Thomas J. Sharpton,
    • Narmada Shenoy,
    • Nihar U. Sheth,
    • Gina A. Simone,
    • Indresh Singh,
    • Christopher S. Smillie,
    • Jack D. Sobel,
    • Daniel D. Sommer,
    • Paul Spicer,
    • Granger G. Sutton,
    • Sean M. Sykes,
    • Diana G. Tabbaa,
    • Mathangi Thiagarajan,
    • Chad M. Tomlinson,
    • Manolito Torralba,
    • Todd J. Treangen,
    • Rebecca M. Truty,
    • Tatiana A. Vishnivetskaya,
    • Jason Walker,
    • Lu Wang,
    • Zhengyuan Wang,
    • Doyle V. Ward,
    • Wesley Warren,
    • Mark A. Watson,
    • Christopher Wellington,
    • Kris A. Wetterstrand,
    • James R. White,
    • Katarzyna Wilczek-Boney,
    • YuanQing Wu,
    • Kristine M. Wylie,
    • Todd Wylie,
    • Chandri Yandava,
    • Liang Ye,
    • Yuzhen Ye,
    • Shibu Yooseph,
    • Bonnie P. Youmans,
    • Lan Zhang,
    • Yanjiao Zhou,
    • Yiming Zhu,
    • Laurie Zoloth,
    • Jeremy D. Zucker,
    • Bruce W. Birren,
    • Richard A. Gibbs,
    • Sarah K. Highlander,
    • Barbara A. Methé,
    • Karen E. Nelson,
    • Joseph F. Petrosino,
    • George M. Weinstock,
    • Richard K. Wilson &
    • Owen White

Contributions

Principal investigators: B.W.B., R.A.G., S.K.H., B.A.M., K.E.N., J.F.P., G.M.W., O.W., R.K.W. Manuscript preparation: D.G., C.H., R.K., O.W. Funding agency management: C.C.B., T.B., V.R.B., J.L.C., S.C., C.D., V.D.F., C.G., M.Y.G., R.D.L., J.M., P.M., J.P., L.M.P., J.A.S., L.W., C.W., K.A.W. Project leadership: S.A., J.H.B., B.W.B., A.T.C., H.H.C., A.M.E., M.G.F., R.S.F., D.G., M.G.G., K.H., S.K.H., C.H., E.A.L., R.M., V.M., J.C.M., B.A.M., M.M., D.M.M., K.E.N., J.F.P., E.J.S., J.V., G.M.W., O.W., A.M.W., K.C.W., J.R.W., S.K.Y., Q.Z. Analysis preparation for manuscript: J.C.C., K.F., D.G., A.G., K.H.H., C.H., R.K., D.K., H.H.K., O.K., K.P.L., R.E.L., J.R., J.F.S., P.D.S., N.S. Data release: L.A., T.B., I.A.C., K.C., H.H.C., N.J.D., D.J.D., A.M.E., V.M.F., L.F., J.M.G., S.G., S.K.H., M.E.H., C.J., V.J., C.K., A.A.M., V.M.M., T.M., M.M., D.M.M., J.O., K.P., J.F.P., C.P., X.Q., R.K.S., N.S., I.S., E.J.S., D.V.W., O.W., K.W., K.C.W., C.Y., B.P.Y., Q.Z. Methods and research development: S.A., H.M.A., M.B., D.M.C., A.M.E., R.L.E., M.F., S.F., M.G.F., D.C.F., D.G., G.G., B.J.H., S.K.H., M.E.H., W.A.K., N.L., K.L., V.M., E.R.M., B.A.M., M.M., D.M.M., C.N., J.F.P., M.E.P., X.Q., M.C.R., C.R., E.J.S., S.M.S., D.G.T., D.V.W., G.M.W., Y.W., K.M.W., S.Y., B.P.Y., S.K.Y., Q.Z. DNA sequence production: S.A., E.A., T.A., T.B., C.J.B., D.A.B., K.D.D., S.P.D., A.M.E., R.L.E., C.N.F., S.F., C.C.F., L.L.F., R.S.F., B.H., S.K.H., M.E.H., V.J., C.L.K., S.L.L., N.L., L.L., D.M.M., I.N., C.N., M.O., J.F.P., X.Q., J.G.R., Y.R., M.C.R., D.V.W., Y.W., B.P.Y., Y.Z. Clinical sample collection: K.M.A., M.A.C., W.M.D., L.L.F., N.G., H.A.H., E.L.H., J.A.K., W.A.K., T.M., A.L.M., P.M., S.M.P., J.F.P., G.A.S., J.V., M.A.W., G.M.W. Body site experts: K.M.A., E.A.V., G.A., L.B., M.J.B., C.C.D., F.E.D., L.F., J.I., J.A.K., S.K.H., H.H.K., K.P.L., P.J.M., J. Ravel, T.M.S., J.A.S., J.D.S., J.V. Ethical, legal and social implications: R.M.F., D.E.H., W.A.K., N.B.K., C.M.L., A.L.M., R.R., P. Sankar, R.R.S., P. Spicer, L.Z. Strain management: E.A.V., J.H.B., I.A.C., K.C., S.W.C., H.H.C., T.Z.D., A.S.D., A.M.E., M.G.F., M.G.G., S.K.H., V.J., N.C.K., S.L.L., L.L., K.L., E.A.L., V.M.M., B.A.M., D.M.M., K.E.N., I.N., I.P., L.S., E.J.S., C.M.T., M.T., D.V.W., G.M.W., A.M.W., Y.W., K.M.W., B.P.Y., L.Z., Y.Z. 16S data analysis: K.M.A., E.J.A., G.L.A., C.A.A., M.B., B.W.B., J.P.B., G.A.B., S.R.C., S.C., J.C., T.Z.D., F.E.D., E.D., A.M.E., R.C.E., K.F., M.F., A.A.F., J.F., H.G., D.G., B.J.H., T.A.H., S.M.H., C.H., J.I., J.K.J., S.T.K., S.K.H., R.K., H.H.K., O.K., P.S.L., R.E.L., K.L., C.A.L., D.M., B.A.M., K.A.M., M.M., M.P., J.F.P., M.P., K.S.P., X.Q., J. Raes, K.P.R., M.C.R., B.R., J.F.S., P.D.S., T.M.S., N.S., J.A.S., W.D.S., T.J.S., C.S.S., E.J.S., R.M.T., J.V., T.A.V., Z.W., D.V.W., G.M.W., J.R.W., K.M.W., Y.Y., S.Y., Y.Z. Shotgun data processing and alignments: C.J.B., J.C.C., E.D., D.G., A.G., M.E.H., H.J., D.K., K.C.K., C.L.K., Y.L., J.C.M., B.A.M., M.M., D.M.M., J.O., J.F.P., X.Q., J.G.R., R.K.S., N.U.S., I.S., E.J.S., G.G.S., S.M.S., J.W., Z.W., G.M.W., O.W., K.C.W., T.W., S.K.Y., L.Z. Assembly: H.M.A., C.J.B., P.S.C., L.C., Y.D., S.P.D., M.G.F., M.E.H., H.J., S.K., B.L., Y.L., C.L., J.C.M., J.M.M., J.R.M., P.J.M., M.M., J.F.P., M.P., M.E.P., X.Q., M.R., R.K.S., M.S., D.D.S., G.G.S., S.M.S., C.M.T., T.J.T., W.W., G.M.W., K.C.W., L.Y., Y.Y., S.K.Y., L.Z. Annotation: O.O.A., V.B., C.J.B., I.A.C., A.T.C., K.C., H.H.C., A.S.D., M.G.G., J.M.G., J.G., A.G., S.G., B.J.H., K.H., S.K.H., C.H., H.J., N.C.K., R.M., V.M.M., K.M., T.M., M.M., J.O., K.P., M.P., X.Q., N.S., E.J.S., G.G.S., S.M.S., M.T., G.M.W., K.C.W., J.R.W., C.Y., S.K.Y., Q.Z., L.Z., W.G.S. Metabolic reconstruction: S.A., B.L.C., J.G., C.H., J.I., B.A.M., M.M., B.R., A.M.S., N.S., M.T., G.M.W., S.Y., Q.Z., J.D.Z.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to:

All data used in this study is available fromtheHuman Microbiome Project Data Analysis and Coordination Center at http://hmpdacc.org and from the NCBI.

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    Supplementary information

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      This file contains Supplementary Methods, a Supplementary Discussion, Supplementary Figures 1-5, Supplementary Table 1 and Supplementary References - see Contents for more details. This file was replaced on 26 June 2012 to correct the caption for Supplementary Figure 4.

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      This zipped file contains Supplementary Tables 2 and 3.

    Comments

    1. Report this comment #45128

      Klaus J. Seelig said:

      This Human Microbiome and Health- Approach indeed is a very helpful and long desired approach to the presently unsolved Interactions between Food and Health.Such is urgently needed, esp.if one considers the great variety of old and new and conventional Fodder- and Feed-Lots and Food-Combinations undeclared for their contents, provenience, uncontrolled for their GMO-Parts' Tolerability and even the herbicidal bits now legally produced in the Food-Plant-Products !
      And all declared as GRAS by some Experts who helped detecting the loopholes in Public Laws which were supposed to safeguard the Health of the Consumer ! And this is all put out (mostly profit-oriented) onto the Market for Consumption by Consumers who may be compared as blindfolded.The Collaterals of this System have just been glimpsed at by the UN-NCD-Forum and the Lobby for putting more speed into this "golden testament proven bizzniss" is happy for the Global Players getting safely settled with their promises in some Low-Cash-Insufficient-Food-Countries. From whence the old wellknown and healthy seeds were confiscated to be returned as altered or 'conditioned' Hybrid Seeds to produce next seasons Cash-Flow-Products. This time for Food, tomorrow for Kerosin-Admixtures, next season as Emergency Fodder only for Animals. And who of their Clients does not obey these rules is to be blamed by his own suffering people. Their Microbiomata will stay unknown, as the causes of babies undernourishment and suddenly dying after the direly needed "Glucose-Injection" (as C4-Glucose).

      And here in our affluent part of the world ? Are the People healthy if they had sufficient of the cheaply produced Mass-products undeclared for the sort of fodder used (because of the price envisioned)? The Facts are Clear: Some are happy that they can produce cheaply en masse which is consumed in spite of the Evidence of 30% of the animals (chicks) dying before the envisioned slaughter-date of less than 3/4 of a year without having seen grass or sunshine. But the meat is oK with the spicy and sweetened additives,

      Another sort of former "Husbandry"(pigs) would not survive twice the time with that fodder anyway, dying of Lipidemia, Liver-and Heart-and Vessel-diseases (formerly only believed to exist as Human Pathology).
      And beef and bulls are fed to be killed before 3 years anyway, while Milk-Production with the energy-dense Fodder brings a Reduction of former Lifetime to the Cows by 75%, which have to be "exchanged" after 7-8 years to avoid Costs of Fodder-, Feedlots- and Stress-induced "Metabolic Diseases".
      But their Meat is "health-promoting" not only for the Pharma-Share-Holders Experimentative and now even Translational Research on Expenses of the National-Health-Systems, even if Cats and Dogs die of it with the same Diabetes as the Rats were known to get before the Big Experiment began of Feeding entire Populations for two Generations with the cheap Commodity. And now those Genes may be undeclared in many "genuine Foods" formerly known to be healthy. But now urgent Research for a Pill is the Problem of the day to avoid the consequences of his Management ?

      The Research into this business which You have started with the Microbiomata is a truely Herculian Project, and Augias Stables have been cleansed by Flodding. Perhaps the insight, that Proprio-Bacteria prepare the animals for costly epidemics and can best grow on their energy-rich fodder used which even goes best in areas where the drinking water taken from the rivers for people and their husbandry is enriched by the NPS with their anyway unretainable but formerly very seldom water products and so help disturbing the primary immune-response drastically. Perhaps this insight comes, if we get the results of what sort of food and water do the Astronauts get to stay healthy in their Lab-Cage aloft. Then perhaps- if the money necessary stays around- we will have a positive result how to produce healthy water and healthy Food to cultivate a functionally optimal Microbioma for to cope with the Bacteria around us. They are just as prone for Mutations as other cells, but by their shorter Generation-time faster adaptable to changes of their Environment, which in their case leads to adaptation by the surviving Bacterial Generations.
      And here the writers fancy rejects to speculate for the comparison of fates.

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