Enterotypes of the human gut microbiome
Open accessAbstract
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.
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Enterotypes define clusters typically dominated by genera like Bacteroides, Prevotella, and Ruminococcus, although subsequent research has sometimes expanded or refined these categories.
“The concept defines clusters typically dominated by genera like Bacteroides, Prevotella, and Ruminococcus, although subsequent research has sometimes expanded or refined these categories.168,169”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [168]
As with known enterotypes, defining taxa included Prevotella, Akkermansia, and Bifidobacterium.
“Concordant with reported enterotypes in the human microbiome47,51,55, we identified microbiotype-defining taxa including Prevotella spp., Akkermansia spp. and Bifidobacterium spp. (Extended Data Fig. 9).”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [47]
The human gut contains several discrete, ecologically balanced communities (microbiotypes) that are resilient but can be changed by diet, drugs, and lifestyle.
“The human gut microbiome includes multiple discrete ecologically balanced communities—hereafter referred to as ‘enteric microbiotypes’—that are resilient although still modifiable by diet, drugs and lifestyle47–52.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [47]
Organizing highly dimensional gut microbiota into discrete ecologically balanced communities or enteric microbiotypes that account for functional and ecological context may improve understanding.
“Complexity of highly dimensional gut microbiota may be better comprehended by organization into discrete classes of ecologically balanced communities or enteric microbiotypes that consider their functional and ecological context47,55.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [47]
Human gut microbiota variation includes discrete clusters or enterotypes, though their distribution may be continuous and composition can vary within an individual.
“Human intestinal microbiota variation encompasses discrete microbial clusters or enterotypes, although their distribution may be continuous and their composition can be variable within the same individual47,50,51.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [47]
The family Prevotellaceae is positively related to SCFA levels in humans and affects spatial learning and memory by modulating neurotransmission and hippocampal synaptic plasticity.
“the family Prevotellaceae has been reported to be positively related to SCFA levels in humans (Arumugam et al., 2011) and affects spatial learning and memory by modulating neurotransmission and hippocampal synaptic plasticity (D’Amato et al., 2020)”
From The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy (2023) · cites this paper as Arumugam et al., 2011
A recent work identified three enterotypes in the human gut microbiome differing in species and functional characteristics.
“A recent work identified three enterotypes in the human gut microbiome differing in species and functional characteristics [5] .”
From Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis (2014) · cites this paper as [5]
The MetaHit consortium proposed that individuals can be classified into enterotypes dominated by Prevotella, Bacteroides, or Ruminococcus.
“The MetaHit consortium has proposed that individuals can be classified as having intestinal microbiota predominantly composed of Prevotella or Bacteroides; a third group has higher proportions of Ruminococcus, compared with the others. These categories have been named “enterotypes”38.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [38]
A greater proportion of Prevotella in the human intestinal microbiota marks residence in an agrarian culture, whereas a greater proportion of Bacteroides is associated with residence in more-industrialized regions.
“a greater proportion of Prevotella in the human intestinal microbiota is a marker of residence in an agrarian culture, whereas a greater proportion of Bacteroides is associated with residence in more-industrialized regions38.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [38]
Diminished Prevotellaceae count is associated with lower level of thiamine and folate biosynthesis as well as lower levels of SCFAs, hydrogen sulfide, and ghrelin.
“Moreover, diminished Prevotellaceae count is associated with lower level of thiamine and folate biosynthesis [423] as well as lower levels of SCFAs, hydrogen sulfide, and ghrelin.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [423]
The distinct groups of TMA-producing gene pools are similar to enterotypes of global intestinal communities.
“similar to enterotypes of global intestinal communities [14]”
From Uncovering the trimethylamine-producing bacteria of the human gut microbiota (2017) · cites this paper as [14]
CntA/B and yeaW/X contribute to TMA generation by converting carnitine into TMA.
“Additional microbial enzyme systems that contribute to TMA generation are now known to include CntA/B and yeaW/X for conversion of carnitine into TMA226–230.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [228]
Under-representation of Prevotellaceae diminishes levels of health-promoting neuroactive short chain fatty acids and the capacity for biosynthesis of thiamine and folate, in line with decreased levels of these vitamins in Parkinson's disease patients.
“The under-representation of Prevotellaceae diminishes the levels of health-promoting neuroactive short chain fatty acids (SCFA) and the capacity for biosynthesis of thiamine and folate (Arumugam et al., 2011), which is in line with decreased levels of these vitamins in PD patients (dos Santos et al., 2009;Luong and Nguyễn, 2013).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Arumugam et al., 2011
It is possible to classify microbiomes by groups of microbial communities or enterotypes, each of which is often dominated by a particular organism.
“It is possible to classify microbiomes by groups of microbial communities or enterotypes, each of which is often dominated by a particular organism [69, 70].”
From Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms (2019) · cites this paper as [69]
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Hoffmann, C., Dollive, S., Grunberg, S., Chen, J., Li, H., Wu, G. D., Lewis, J. D., & Bushman, F. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066019 · Cited by 808 · see citing works
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
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The Gut Microbiota Plays a Protective Role in the Host Defence Against Pneumococcal Pneumonia
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- Authors
- MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., Batto, J.-M., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H. B., Nielsen, T., Pons, N., Poulain, J., Qin, J., Sicheritz-Ponten, T., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E. G., Wang, J., Guarner, F., Pedersen, O., de Vos, W. M., Brunak, S., Doré, J., Weissenbach, J., Ehrlich, S. D., & Bork, P.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Vrije Universiteit Brussel (BE)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Technical University of Denmark (DK)
- Vall d'Hebron Hospital Universitari (ES)
- University of Copenhagen (DK)
- The University of Tokyo (JP)
- University of Miyazaki (JP)
- Wageningen University & Research (NL)
- Tokyo Institute of Technology (JP)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- BGI Group (China) (CN)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Ehrlich, S. Dusko
- ORCID
- Arumugam, Manimozhiyan
- Raes, Jeroen
- Yamada, Takuji
- Mende, Daniel R.
- Tap, Julien
- Borruel, Natalia
- Casellas, Francesc
- Gautier, Laurent
- Hansen, Torben
- Hattori, Masahira
- Hayashi, Tetsuya
- Kleerebezem, Michiel
- Kurokawa, Ken
- Leclerc, Marion
- Manichanh, Chaysavanh
- Nielsen, H. Bjørn
- Nielsen, Trine
- Pons, Nicolas
- Poulain, Julie
- Qin, Junjie
- Tims, Sebastian
- Torrents, David
- Zoetendal, Erwin G.
- Wang, Jun
- Guarner, Francisco
- Pedersen, Oluf
- Brunak, Søren
- Weissenbach, Jean
- Ehrlich, S. Dusko
- Venue
- Nature
- Published
- 2011-04-20
- Volume
- 473
- Issue
- 7346
- Pages
- 174-180
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3728647
- OpenAlex
- W2032230795
- Cited by
- 7,548
- References
- 70
- Citations by year
- 2026: 312 · 2025: 499 · 2024: 617 · 2023: 654 · 2022: 629 · 2021: 669 · 2020: 583 · 2019: 558 · 2018: 443 · 2017: 416 · 2016: 425 · 2015: 409 · 2014: 425 · 2013: 419 · 2012: 365
- FWCI
- 172.79
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- europepmc.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Socio-Environmental Systems Modeling (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (076964, 082372)
- Novo Nordisk Fonden (NNF10CC1016517)
- Japan Society for the Promotion of Science (221S0002)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK002800)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Keywords
- enterotypes, human gut microbiome, microbial community clustering, host-microbe symbiosis, body mass index, cross-cohort validation, microbial biomarkers
- MeSH terms
- Bacteria, Europe, Feces, Female, Humans, Intestines, Male, Phylogeny, Bacterial Typing Techniques, Biomarkers, Biodiversity, Metagenome, Metagenomics
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