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Enterotypes of the human gut microbiome

Author

Listed:
  • Manimozhiyan Arumugam

    (European Molecular Biology Laboratory, Meyerhofstrasse 1)

  • Jeroen Raes

    (European Molecular Biology Laboratory, Meyerhofstrasse 1
    VIB—Vrije Universiteit Brussel)

  • Eric Pelletier

    (Commissariat à l’Energie Atomique, Genoscope
    Centre National de la Recherche Scientifique, UMR8030
    Université d'Evry Val d'Essone 91000 Evry)

  • Denis Le Paslier

    (Commissariat à l’Energie Atomique, Genoscope
    Centre National de la Recherche Scientifique, UMR8030
    Université d'Evry Val d'Essone 91000 Evry)

  • Takuji Yamada

    (European Molecular Biology Laboratory, Meyerhofstrasse 1)

  • Daniel R. Mende

    (European Molecular Biology Laboratory, Meyerhofstrasse 1)

  • Gabriel R. Fernandes

    (European Molecular Biology Laboratory, Meyerhofstrasse 1
    Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte)

  • Julien Tap

    (European Molecular Biology Laboratory, Meyerhofstrasse 1
    Institut National de la Recherche Agronomique)

  • Thomas Bruls

    (Commissariat à l’Energie Atomique, Genoscope
    Centre National de la Recherche Scientifique, UMR8030
    Université d'Evry Val d'Essone 91000 Evry)

  • Jean-Michel Batto

    (Institut National de la Recherche Agronomique)

  • Marcelo Bertalan

    (Center for Biological Sequence Analysis, Technical University of Denmark)

  • Natalia Borruel

    (Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd)

  • Francesc Casellas

    (Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd)

  • Leyden Fernandez

    (Barcelona Supercomputing Center, Jordi Girona 31)

  • Laurent Gautier

    (Center for Biological Sequence Analysis, Technical University of Denmark)

  • Torben Hansen

    (Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen
    Faculty of Health Sciences, University of Southern Denmark)

  • Masahira Hattori

    (Computational Biology Laboratory Bld, The University of Tokyo Kashiwa Campus, Kashiwa-no-ha 5-1-5, Kashiwa)

  • Tetsuya Hayashi

    (Frontier Science Research Center, University of Miyazaki, 5200 Kiyotake)

  • Michiel Kleerebezem

    (Laboratory of Microbiology, Wageningen University)

  • Ken Kurokawa

    (Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi)

  • Marion Leclerc

    (Institut National de la Recherche Agronomique)

  • Florence Levenez

    (Institut National de la Recherche Agronomique)

  • Chaysavanh Manichanh

    (Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd)

  • H. Bjørn Nielsen

    (Center for Biological Sequence Analysis, Technical University of Denmark)

  • Trine Nielsen

    (Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen)

  • Nicolas Pons

    (Institut National de la Recherche Agronomique)

  • Julie Poulain

    (Commissariat à l’Energie Atomique, Genoscope)

  • Junjie Qin

    (BGI-Shenzhen)

  • Thomas Sicheritz-Ponten

    (Center for Biological Sequence Analysis, Technical University of Denmark
    Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark)

  • Sebastian Tims

    (Laboratory of Microbiology, Wageningen University)

  • David Torrents

    (Barcelona Supercomputing Center, Jordi Girona 31
    Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23)

  • Edgardo Ugarte

    (Commissariat à l’Energie Atomique, Genoscope)

  • Erwin G. Zoetendal

    (Laboratory of Microbiology, Wageningen University)

  • Jun Wang

    (BGI-Shenzhen
    University of Copenhagen)

  • Francisco Guarner

    (Digestive System Research Unit, University Hospital Vall d’Hebron, Ciberehd)

  • Oluf Pedersen

    (Marie Krogh Center for Metabolic Research, Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen
    Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen
    Hagedorn Research Institute
    Faculty of Health Sciences, University of Aarhus)

  • Willem M. de Vos

    (Laboratory of Microbiology, Wageningen University
    University of Helsinki)

  • Søren Brunak

    (Center for Biological Sequence Analysis, Technical University of Denmark)

  • Joel Doré

    (Institut National de la Recherche Agronomique)

  • Jean Weissenbach

    (Commissariat à l’Energie Atomique, Genoscope
    Centre National de la Recherche Scientifique, UMR8030
    Université d'Evry Val d'Essone 91000 Evry)

  • S. Dusko Ehrlich

    (Institut National de la Recherche Agronomique)

  • Peer Bork

    (European Molecular Biology Laboratory, Meyerhofstrasse 1
    Max Delbrück Centre for Molecular Medicine)

Abstract

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.

Suggested Citation

  • Manimozhiyan Arumugam & Jeroen Raes & Eric Pelletier & Denis Le Paslier & Takuji Yamada & Daniel R. Mende & Gabriel R. Fernandes & Julien Tap & Thomas Bruls & Jean-Michel Batto & Marcelo Bertalan & Na, 2011. "Enterotypes of the human gut microbiome," Nature, Nature, vol. 473(7346), pages 174-180, May.
  • Handle: RePEc:nat:nature:v:473:y:2011:i:7346:d:10.1038_nature09944
    DOI: 10.1038/nature09944
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    2. Julien Tap & Franck Lejzerowicz & Aurélie Cotillard & Matthieu Pichaud & Daniel McDonald & Se Jin Song & Rob Knight & Patrick Veiga & Muriel Derrien, 2023. "Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Mendler, Isabella-Hilda & Drossel, Barbara & Hütt, Marc-Thorsten, 2024. "Microbiome abundance patterns as attractors and the implications for the inference of microbial interaction networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 639(C).
    4. Oliver Aasmets & Kertu Liis Krigul & Kreete Lüll & Andres Metspalu & Elin Org, 2022. "Gut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
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    7. Courtney M. Thomas & Elie Desmond-Le Quéméner & Simonetta Gribaldo & Guillaume Borrel, 2022. "Factors shaping the abundance and diversity of the gut archaeome across the animal kingdom," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. M. C. Rühlemann & C. Bang & J. F. Gogarten & B. M. Hermes & M. Groussin & S. Waschina & M. Poyet & M. Ulrich & C. Akoua-Koffi & T. Deschner & J. J. Muyembe-Tamfum & M. M. Robbins & M. Surbeck & R. M. , 2024. "Functional host-specific adaptation of the intestinal microbiome in hominids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Emidio Scarpellini & Emanuele Rinninella & Martina Basilico & Esther Colomier & Carlo Rasetti & Tiziana Larussa & Pierangelo Santori & Ludovico Abenavoli, 2021. "From Pre- and Probiotics to Post-Biotics: A Narrative Review," IJERPH, MDPI, vol. 19(1), pages 1-14, December.
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    11. Zhiguang Qiu & Li Yuan & Chun-Ang Lian & Bin Lin & Jie Chen & Rong Mu & Xuejiao Qiao & Liyu Zhang & Zheng Xu & Lu Fan & Yunzeng Zhang & Shanquan Wang & Junyi Li & Huiluo Cao & Bing Li & Baowei Chen & , 2024. "BASALT refines binning from metagenomic data and increases resolution of genome-resolved metagenomic analysis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Elio L Herzog & Melania Wäfler & Irene Keller & Sebastian Wolf & Martin S Zinkernagel & Denise C Zysset-Burri, 2021. "The importance of age in compositional and functional profiling of the human intestinal microbiome," PLOS ONE, Public Library of Science, vol. 16(10), pages 1-13, October.
    13. Zachary D. Wallen & Ayse Demirkan & Guy Twa & Gwendolyn Cohen & Marissa N. Dean & David G. Standaert & Timothy R. Sampson & Haydeh Payami, 2022. "Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    14. Laura Sanchis-Artero & Juan Francisco Martínez-Blanch & Sergio Manresa-Vera & Ernesto Cortés-Castell & Josefa Rodriguez-Morales & Xavier Cortés-Rizo, 2020. "Evaluation of Changes in Gut Microbiota in Patients with Crohn’s Disease after Anti-Tnfα Treatment: Prospective Multicenter Observational Study," IJERPH, MDPI, vol. 17(14), pages 1-14, July.
    15. Doris Vandeputte & Lindsey Commer & Raul Y. Tito & Gunter Kathagen & João Sabino & Séverine Vermeire & Karoline Faust & Jeroen Raes, 2021. "Temporal variability in quantitative human gut microbiome profiles and implications for clinical research," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    16. Kihyun Lee & Sebastien Raguideau & Kimmo Sirén & Francesco Asnicar & Fabio Cumbo & Falk Hildebrand & Nicola Segata & Chang-Jun Cha & Christopher Quince, 2023. "Population-level impacts of antibiotic usage on the human gut microbiome," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    17. Georges P. Schmartz & Jacqueline Rehner & Madline P. Gund & Verena Keller & Leidy-Alejandra G. Molano & Stefan Rupf & Matthias Hannig & Tim Berger & Elias Flockerzi & Berthold Seitz & Sara Fleser & Sa, 2024. "Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Roger S. Fujioka & Helena M. Solo-Gabriele & Muruleedhara N. Byappanahalli & Marek Kirs, 2015. "U.S. Recreational Water Quality Criteria: A Vision for the Future," IJERPH, MDPI, vol. 12(7), pages 1-25, July.
    19. Diego E. Sastre & Nazneen Sultana & Marcos V. A. S. Navarro & Maros Huliciak & Jonathan Du & Javier O. Cifuente & Maria Flowers & Xu Liu & Pete Lollar & Beatriz Trastoy & Marcelo E. Guerin & Eric J. S, 2024. "Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Feng Tong & Teng Wang & Na L. Gao & Ziying Liu & Kuiqing Cui & Yiqian Duan & Sicheng Wu & Yuhong Luo & Zhipeng Li & Chengjian Yang & Yixue Xu & Bo Lin & Liguo Yang & Alfredo Pauciullo & Deshun Shi & G, 2022. "The microbiome of the buffalo digestive tract," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    21. Aarthi Ravikrishnan & Indrik Wijaya & Eileen Png & Kern Rei Chng & Eliza Xin Pei Ho & Amanda Hui Qi Ng & Ahmad Nazri Mohamed Naim & Jean-Sebastien Gounot & Shou Ping Guan & Jasinda Lee Hanqing & Lihua, 2024. "Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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