Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host–microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
An author was omitted. His name has been added to the HTML and PDF and described in the accompanying Corrigendum.
The authors are grateful to C. Creevey, G. Falony and members of the Bork group at EMBL for discussions and assistance. We thank the EMBL IT core facility and Y. Yuan for managing the high-performance computing resources. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013): MetaHIT, grant agreement HEALTH-F4-2007-201052, EMBL, the Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCAMP), Novo Nordisk Foundation and the International Science and Technology Cooperation Project in China (0806). Obese/non-obese volunteers for the MicroObes study were recruited from the SU.VI.MAX cohort study coordinated by P. Galan and S. Hercberg, and metagenome sequencing was funded by Agence Nationale de la Recherche (ANR); volunteers for MicroAge study were recruited from the CROWNALIFE cohort study coordinated by S. Silvi and A. Cresci, and metagenome sequencing was funded by GenoScope. Ciberehd is funded by the Instituto de Salud Carlos III (Spain). J.R. is supported by the Institute for the encouragement of Scientific Research and Innovation of Brussels (ISRIB) and the Odysseus programme of the Fund for Scientific Research Flanders (FWO). We are thankful to the Human Microbiome Project for generating the reference genomes from human gut microbes and the International Human Microbiome Consortium for discussions and exchange of data.
Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd, 08035 Barcelona, Spain.
Commissariat à l’Energie Atomique, Genoscope, 91000 Evry, France.
Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France.
UCB Pharma SA, 28046 Madrid, Spain.
Danone Research, 91120 Palaiseau, France.
Heidelberger Strasse 24, 64285 Darmstadt, Germany.
Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark.
Institute of Genetics and Molecular and Cellular Biology, CNRS, INSERM, University of Strasbourg, 67404 Illkrich, France.
The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Istituto Europeo di Oncologia, 20100 Milan, Italy.
Institut Mérieux, 17 rue Burgelat, 69002 Lyon, France.
Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
All authors are members of the Metagenomics of the Human Intestinal Tract (MetaHIT) Consortium. Jun W., F.G., O.P., W.M.d.V., S.B., J.D., Jean W., S.D.E. and P.B. managed the project. N.B., F.C., T.H., C.M. and T. N. performed clinical analyses. M.L. and F.L. performed DNA extraction. E.P., D.L.P., T.B., J.P. and E.U. performed DNA sequencing. M.A., J.R., S.D.E. and P.B. designed the analyses. M.A., J.R., T.Y., D.R.M., G.R.F., J.T., J.-M.B., M.B., L.F., L.G., M.K., H.B.N., N.P., J.Q., T.S.-P., S.T., D.T., E.G.Z., S.D.E. and P.B. performed the analyses. M.A., J.R., P.B. and S.D.E. wrote the manuscript. M.H., T.H., K.K. and the MetaHIT Consortium members contributed to the design and execution of the study.
Correspondence to S. Dusko Ehrlich or Peer Bork.
Raw Sanger read data from the European faecal metagenomes have been deposited in the NCBI Trace Archive with the following project identifiers: MH6 (33049), MH13 (33053), MH12 (33055), MH30 (33057), CD1 (33059), CD2 (33061), UC4 (33113), UC6 (33063), NO1 (33305), NO3 (33307), NO4 (33309), NO8 (33311), OB2 (33313), OB1 (38231), OB6 (38233), OB8 (45929), A (63073), B (63075), C (63077), D (63079), E (63081), G (63083). Contigs, genes and annotations are available to download from http://www.bork.embl.de/Docu/Arumugam_et_al_2011/.
The file contains Supplementary Methods, Supplementary Notes and Supplementary References. A minor error in Supplementary Information section 2.2 was corrected on 02 June 2011.
This file contains Supplementary Figures 1-27 with legends.
The file contains Supplementary Tables 1 - 2 and 4 - 24 (see separate file for Supplementary Table 3).
The file contains Supplementary Table 3.
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.