Abstract

Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the concept of enterotypes, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into functional, ecological and medical contexts. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.

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Change history

  • Correction 13 February 2018

    In the version of this Perspective originally published, the first and last name of co-author Manimozhiyan Arumugam were switched. This has now been corrected in all versions of the Perspective.

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Acknowledgements

The authors are grateful to the members of the Bork group at EMBL for discussions and assistance. The research leading to these results has received funding from EMBL, the VIB, the Rega institute for Medical Research, the European Research Council via the CancerBiome project (project reference 268985), MicrobesInside (250172) and the European Community’s Seventh Framework Programme via the MetaHIT (HEALTH-F4-2007-201052), the METACARDIS project (FP7-HEALTH-2012-INNOVATION-I-305312), the European Union’s Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant 600375), Metagenopolis grant ANR-11-DPBS-0001 and the IHMS project (FP7-HEALTH-2010-single-stage-261376).

Author information

Author notes

  1. Paul I. Costea and Falk Hildebrand contributed equally to this work.

Affiliations

  1. European Molecular Biology Laboratory, Heidelberg, Germany

    • Paul I. Costea
    • , Falk Hildebrand
    • , Shinichi Sunagawa
    • , Georg Zeller
    •  & Peer Bork
  2. VIB Center for Microbiology, VIB, Belgium

    • Falk Hildebrand
    •  & Jeroen Raes
  3. Laboratory of Microbiology, Vrije Universiteit Brussel, Brussels, Belgium

    • Falk Hildebrand
    •  & Jeroen Raes
  4. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Manimozhiyan Arumugam
  5. Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    • Fredrik Bäckhed
    •  & Jun Wang
  6. Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    • Fredrik Bäckhed
  7. New York University Langone Medical Center, New York, NY, USA

    • Martin J. Blaser
  8. Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    • Frederic D. Bushman
  9. RPU Immunobiology, Department of Bacteriology & Immunology, University of Helsinki, Helsinki, Finland

    • Willem M. de Vos
  10. Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands

    • Willem M. de Vos
  11. Metagenopolis, Institut National de la Recherche Agronomique, Jouy en Josas, France

    • S. Dusko Ehrlich
  12. King’s College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, London, UK

    • S. Dusko Ehrlich
  13. Institute for Genome Sciences at the University of Maryland School of Medicine, Baltimore, MD, USA

    • Claire M. Fraser
  14. Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan

    • Masahira Hattori
  15. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    • Curtis Huttenhower
  16. APC Microbiome Institute, University College Cork, Cork, Ireland

    • Ian B. Jeffery
    • , Paul W. O’Toole
    •  & Fergus Shanahan
  17. Biotechnology Institute, University of Minnesota, Saint Paul, MN, USA

    • Dan Knights
  18. Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA

    • Dan Knights
  19. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • James D. Lewis
  20. MPI Department of Microbiome Science, Tübingen, Germany

    • Ruth E. Ley
  21. Department of Integrative Biology, University of Texas, Austin, TX, USA

    • Howard Ochman
  22. Warwick Medical School, University of Warwick, Coventry, UK

    • Christopher Quince
  23. Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA

    • David A. Relman
  24. Department of Medicine, Stanford University, Stanford, CA, USA

    • David A. Relman
  25. Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA

    • David A. Relman
  26. Department of Biology, Institute of Microbiology, ETH Zurich, Zurich, Switzerland

    • Shinichi Sunagawa
  27. Department of Biology, University of Copenhagen, Copenhagen, Denmark

    • Jun Wang
  28. Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia

    • Jun Wang
  29. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau, China

    • Jun Wang
  30. Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Pokfulam, Hong Kong

    • Jun Wang
  31. The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA

    • George M. Weinstock
  32. Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Gary D. Wu
  33. Ministry of Education Key Laboratory for Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

    • Liping Zhao
  34. Department of Microbiology and Immunology, Rega Institute KU Leuven, Leuven, Belgium

    • Jeroen Raes
  35. Department of Computer Science, University of Colorado, Boulder, CO, USA

    • Rob Knight
  36. Biofrontiers Institute, University of Colorado, Boulder, CO, USA

    • Rob Knight
  37. Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA

    • Rob Knight
  38. Howard Hughes Medical Institute, University of Colorado, Boulder, CO, USA

    • Rob Knight
  39. Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany

    • Peer Bork
  40. Molecular Medicine Partnership Unit, Heidelberg, Germany

    • Peer Bork

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Contributions

P.B., R.K. and J.R. conceived the review. P.I.C., F.H. and G.Z. performed data analysis. F.H., P.I.C., J.R. and P.B. performed the literature research, with input from all co-authors. P.I.C., F.H., S.S., R.K., J.R. and P.B. wrote the manuscript with contributions from M.A., F.B., M.J.B., F.D.B., W.M.d.V., S.D.E., C.m.F., M.H., C.H., I.B.J., D.K., J.D.L., R.E.L., H.O., P.W.O., C.Q., D.A.R., F.S., J.W., G.M.W., G.D.W., G.Z. and L.Z.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jeroen Raes or Rob Knight or Peer Bork.

Supplementary information

  1. Supplementary Information

    Supplementary Methods, Tables, Figures and References.

  2. Supplementary Table 3

    Functional differences between three different enterotype models.

  3. Supplementary Table 4

    Associations between obesity-related parameters.

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https://doi.org/10.1038/s41564-017-0072-8

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