Subjects

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.

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Accessions

European Nucleotide Archive

Data deposits

The raw Illumina read data for all samples has been deposited in the EBI European Nucleotide Archive under the accession number ERP003612.

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Acknowledgements

The authors wish to thank A. Forman, T. Lorentzen, B. Andreasen, G. J. Klavsen and M. M. Andersen for technical assistance; A. L. Nielsen, G. Lademann and M. M. H. Kristensen for management assistance, K. Kiil for discussions and assistance, and A. Walker for comments on the manuscript. This research has received funding from European Community’s Seventh Framework Program (FP7/2007-2013): MetaHIT, grant agreement HEALTH-F4-2007-201052. Additional funding came from The Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp, http://www.lucamp.org), ANR MicroObes, the Metagenopolis grant ANR-11-DPBS-0001, Region Ile de France (CODDIM) and Fondacoeur. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk).

Author information

Author notes

    • Emmanuelle Le Chatelier
    • , Trine Nielsen
    • , Junjie Qin
    •  & Edi Prifti

    These authors contributed equally to this work.

Affiliations

  1. INRA, Institut National de la Recherche Agronomique, US1367 Metagenopolis, 78350 Jouy en Josas, France

    • Emmanuelle Le Chatelier
    • , Edi Prifti
    • , Mathieu Almeida
    • , Jean-Michel Batto
    • , Sean Kennedy
    • , Pierre Leonard
    • , Florence Levenez
    • , Nicolas Pons
    • , Julien Tap
    • , Joël Doré
    •  & S. Dusko Ehrlich
  2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    • Trine Nielsen
    • , Manimozhiyan Arumugam
    • , Kristoffer Burgdorf
    • , Niels Grarup
    • , Torben Hansen
    •  & Oluf Pedersen
  3. BGI-Shenzhen, Shenzhen 518083, China

    • Junjie Qin
    • , Manimozhiyan Arumugam
    • , Junhua Li
    •  & Jun Wang
  4. Department of Structural Biology, VIB, Pleinlaan 2, 1050 Brussels, Belgium

    • Falk Hildebrand
    • , Gwen Falony
    •  & Jeroen Raes
  5. Department of Bioscience Engineering, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium

    • Falk Hildebrand
    • , Gwen Falony
    •  & Jeroen Raes
  6. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany

    • Manimozhiyan Arumugam
    • , Shinichi Sunagawa
    • , Julien Tap
    •  & Peer Bork
  7. School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, China

    • Junhua Li
  8. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2900 Glostrup, Denmark

    • Torben Jørgensen
  9. Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    • Torben Jørgensen
  10. Institute of Public Health, Faculty of Medicine, University of Aalborg, DK-9100 Aalborg, Denmark

    • Torben Jørgensen
  11. Department of Clinical Biochemistry, Vejle Hospital, DK-7100 Vejle, Denmark

    • Ivan Brandslund
  12. Institute of Regional Health Research, University of Southern Denmark, DK-8200 Odense, Denmark

    • Ivan Brandslund
  13. Center for Biological Sequence Analysis & Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

    • Henrik Bjørn Nielsen
    • , Agnieszka S. Juncker
    • , Marcelo Bertalan
    • , Simon Rasmussen
    • , Søren Brunak
    •  & Thomas Sicheritz-Ponten
  14. Laboratory of Microbiology, Wageningen University, 6710BA Ede, The Netherlands

    • Sebastian Tims
    • , Erwin G. Zoetendal
    • , Michiel Kleerebezem
    •  & Willem M. de Vos
  15. Institut National de la Santé et de la Recherche Médicale, U 872, Nutriomique, Équipe 7, Centre de Recherches des Cordeliers, 75006 Paris, France

    • Karine Clément
    •  & Jean-Daniel Zucker
  16. Université Pierre et Marie-Curie-Paris VI, 75006 Paris, France

    • Karine Clément
    •  & Jean-Daniel Zucker
  17. Assistance Publique-Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, CRNH-Ile de France, Pitié-Salpêtrière, 75013 Paris, France

    • Karine Clément
  18. INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, 78350 Jouy en Josas, France

    • Joël Doré
    •  & Pierre Renault
  19. Department of Biology, Ole Maaløes Vej 5, University of Copenhagen, DK-2200 Copenhagen, Denmark

    • Karsten Kristiansen
    •  & Jun Wang
  20. Department of Bacteriology and Immunology, University of Helsinki, FIN-00014 Finland

    • Willem M. de Vos
  21. Institut de Recherche pour le Développement, UMI 209, Unité de modélisation mathématique et informatique des Systèmes Complexes, F-93143 Bondy, France

    • Jean-Daniel Zucker
  22. Faculty of Health Sciences, University of Southern Denmark, DK-8200 Odense, Denmark

    • Torben Hansen
  23. King Abdulazziz University, Jeddah 21589, Saudi Arabia

    • Jun Wang
  24. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark

    • Jun Wang
  25. Center for Sequencing Aarhus University, DK-8000 Aarhus C, Denmark

    • Jun Wang
  26. Hagedorn Research Institute, DK-2820 Gentofte, Denmark

    • Oluf Pedersen
  27. Institute of Biomedical Science, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    • Oluf Pedersen
  28. Faculty of Health, Aarhus University, DK-8000 Aarhus, Denmark

    • Oluf Pedersen
  29. INRA, Institut National de la Recherche Agronomique, UMR 14121 MICALIS, 78350 Jouy en Josas, France.

    • Eric Guedon
    • , Christine Delorme
    • , Séverine Layec
    • , Ghalia Khaci
    • , Maarten van de Guchte
    • , Gaetana Vandemeulebrouck
    • , Alexandre Jamet
    • , Rozenn Dervyn
    • , Nicolas Sanchez
    • , Emmanuelle Maguin
    • , Yohanan Winogradski
    • , Antonella Cultrone
    • , Marion Leclerc
    • , Catherine Juste
    •  & Hervé Blottière
  30. INRA, Institut National de la Recherche Agronomique, US1367 Metagenopolis, 78350 Jouy en Josas, France.

    • Florence Haimet
    •  & Hervé Blottière
  31. Commissariat à l’Energie Atomique, Genoscope, 91000 Evry, France.

    • Eric Pelletier
    • , Denis LePaslier
    • , François Artiguenave
    • , Thomas Bruls
    •  & Jean Weissenbach
  32. Centre National de la Recherche Scientifique, UMR8030, 91000 Evry, France.

    • Eric Pelletier
    • , Denis LePaslier
    • , François Artiguenave
    • , Thomas Bruls
    •  & Jean Weissenbach
  33. Evry, France, Université d’Evry Val d’Essone. 91000 Evry, France.

    • Eric Pelletier
    • , Denis LePaslier
    • , François Artiguenave
    • , Thomas Bruls
    •  & Jean Weissenbach
  34. The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

    • Keith Turner
    •  & Julian Parkhill
  35. Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd, 08035 Barcelona, Spain.

    • Maria Antolin
    • , Chaysavanh Manichanh
    • , Francesc Casellas
    • , Natalia Boruel
    • , Encarna Varela
    • , Antonio Torrejon
    •  & Francisco Guarner
  36. Danone Research, 91120 Palaiseau, France.

    • Gérard Denariaz
    • , Muriel Derrien
    • , Johan E. T. van Hylckama Vlieg
    •  & Patrick Veiga
  37. Gut Biology & Microbiology, Danone Research, Centre for Specialized Nutrition, Bosrandweg 20, 6704 PH Wageningen, The Netherlands.

    • Raish Oozeer
    •  & Jan Knol
  38. Istituto Europeo di Oncologia, 20100 Milan, Italy.

    • Maria Rescigno
  39. Institut Mérieux, 17 rue Burgelat, 69002 Lyon, France.

    • Christian Brechot
    • , Christine M’Rini
    •  & Alexandre Mérieux
  40. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.

    • Takuji Yamada

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  1. MetaHIT consortium

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Contributions

O.P. and S.D.E. designed the study, O.P., S.D.E., P.B., W.J., S.B., K.C., J.D., M.K., P.R., T.S.-P., W.M.d.V., T.H., J.R. and K.K. managed the study. T.N., K.B., T.H., N.G., T.J., I.B. and O.P. carried out patient phenotyping and clinical data analyses. T.N., K.B. and F.L. performed sample collection and DNA extraction. J.Q. and J.L. supervised DNA sequencing and gene profiling. S.D.E. and O.P. designed and supervised the data analyses. E.L.C., E.P., T.N., N.G., G.F., F.H., M.Al., M.Ar., J.-M.B., S.K., P.L., N.P., S.S., J.T., J.Q., J.L., J.-D.Z., S.R. and S.D.E. performed the data analyses. S.T. and E.G.Z. carried out HITChip analysis. M.B., A.S.J., H.B.N. and T.S.-P. carried out metagenomic array analyses. S.D.E., O.P., J.R. and P.B. wrote the paper. MetaHIT consortium members provided creative environment and constructive criticism throughout the study.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Peer Bork or Jun Wang or S. Dusko Ehrlich or Oluf Pedersen.

Supplementary information

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    Supplementary Information

    This file contains Supplementary Figures 1-12 and Supplementary Tables 8-9.

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    Supplementary Data

    This file contains Supplementary Tables 1-7 and 10-11.

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