Structure, function and diversity of the healthy human microbiome

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, Elizabeth A. Lobos, Ramana Madupu, Vincent Magrini, John C. Martin, Makedonka Mitreva, Donna M. Muzny, Erica J. Sodergren, James VersalovicAye M. Wollam, Kim C. Worley, Jennifer R. Wortman, Sarah K. Young, Qiandong Zeng, Kjersti M. Aagaard, Olukemi O. Abolude, Emma Allen-Vercoe, Eric J. Alm, Lucia Alvarado, Gary L. Andersen, Scott Anderson, Elizabeth Appelbaum, Harindra M. Arachchi, Gary Armitage, Cesar A. Arze, Tulin Ayvaz, Carl C. Baker, Lisa Begg, Tsegahiwot Belachew, Veena Bhonagiri, Monika Bihan, Martin J. Blaser, Toby Bloom, Vivien Bonazzi, J. Paul Brooks, Gregory A. Buck, Christian J. Buhay, Dana A. Busam, Joseph L. Campbell, Shane R. Canon, Brandi L. Cantarel, Patrick S.G. Chain, I. Min A. Chen, Lei Chen, Shaila Chhibba, Ken Chu, Dawn M. Ciulla, Jose C. Clemente, Sandra W. Clifton, Sean Conlan, Jonathan Crabtree, Mary A. Cutting, Noam J. Davidovics, Catherine C. Davis, 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 Oglaughlin, 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

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7987 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalNature
Volume486
Issue number7402
DOIs
StatePublished - Jun 14 2012

Bibliographical note

Funding Information:
Acknowledgements The Consortium would like to thank our external scientific advisory board: R. Blumberg, J. Davies, R. Holt, P. Ossorio, F. Ouellette, G. Schoolnik and A. Williamson. We would also like to thank our collaborators throughout the International Human Microbiome Consortium, particularly the investigators of the MetaHIT project, for advancing human microbiome research. Data repository management was provided by the National Center for Biotechnology Information and the Intramural Research Program of the NIH National Library of Medicine. We appreciate the participation of the individuals from the Saint Louis, Missouri, and Houston, Texas areas who made this study possible. This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon& Betty Moore Foundationfunding and institutionalfunding from the J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMP data was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University.

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