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Environment dominates over host genetics in shaping human gut microbiota
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Abstract
Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.
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“This can be attributed to the highly individual-specificity of the human microbiome,10,11 shaped by genetics, diet, age, geography, disease status, and intrinsic host factors.12”
From Gut microbiota drives structural variation of exogenous probiotics to enhance colonization (2025) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“adult microbial communities seem to be predominantly shaped by prior stochastic environmental exposures, as well as multiple other factors such as diet, antibiotic therapy and host genetics, with direct 'inheritance' from the mother at birth playing a lesser role.”
From Human microbiome myths and misconceptions (2023) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“proportionally few microbiota species are truly 'heritable' and persist through from birth to adulthood in the offspring 15,16 .”
From Human microbiome myths and misconceptions (2023) · cites this paper as [16]
Experimental — accuracy not yet measuredIn the citing paper
“Diet has emerged as a driving factor in microbiota composition and function (Flint et al., 2017; Muegge et al., 2011; Rothschild et al., 2018; Zhernakova et al., 2016).”
From Gut-microbiota-targeted diets modulate human immune status (2021) · cites this paper as Rothschild et al., 2018
In the citing paper
“However, the effect size is likely small given recent microbial-genetic association studies showing environmental factors to have substantially greater impact on the gut microbiome than genetics22.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [22]
In the citing paper
“Genome-wide analyses estimate that host variants account for roughly 2%–8% of interindividual compositional variation,58,59”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [59]
In the citing paper
“Together, they explain nearly 20% of interindividual variation in microbial composition, with drugs often exerting the stronger influence.59,70”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [59]
In the citing paper
“with host genetics accounting for <10% of variation (14).”
From Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response (2021) · cites this paper as [14]
In the citing paper
“Despite the low number of samples, these results suggest that the environment has more influence on the gut microbiome than the pathological condition, which is in accordance with recent findings 22,23 .”
From Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice (2019) · cites this paper as [22]
In the citing paper
“Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability.”
From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [4]
In the citing paper
“Besides diet, the gut microbiota is shaped by a combination of extrinsic (e.g., lifestyle and medication) and intrinsic (e.g., host genetics, immune and metabolic regulations) factors. It is generally acknowledged that the extrinsic factors elicit the predominant effect, with diet the most widely studied [4].”
From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [4]
In the citing paper
“Diet is thought to explain over 50% of these microbial structural variations in mice and 20% in humans signalling the potential for dietary strategies in disease management through gut microbiota modulation [3,4].”
From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [4]
In the citing paper
“The gut microbiome is shaped by a wealth of environmental factors whose impacts dominate over host genetics.126”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [126]
In the citing paper
“host-genetic influences on gut microbiome composition (Goodrich et al., 2016;Rothschild et al., 2018) are also likely to play a role in influencing the rate and extent of microbial xenobiotic metabolism.”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Rothschild et al., 2018
In the citing paper
“and alternately, estimating that host genetics explain only a minor percentage of microbiome variation [69].”
From Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana (2019) · cites this paper as [69]
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Metadata
- Authors
- Rothschild, D., Weissbrod, O., Barkan, E., Kurilshikov, A., Korem, T., Zeevi, D., Costea, P. I., Godneva, A., Kalka, I. N., Bar, N., Shilo, S., Lador, D., Vila, A. V., Zmora, N., Pevsner-Fischer, M., Israeli, D., Kosower, N., Malka, G., Wolf, B. C., Avnit-Sagi, T., Lotan-Pompan, M., Weinberger, A., Halpern, Z., Carmi, S., Fu, J., Wijmenga, C., Zhernakova, A., Elinav, E., & Segal, E.
- Affiliations
- Weizmann Institute of Science (IL)
- University Medical Center Groningen (NL)
- Tel Aviv University (IL)
- Jerusalem Mental Health Center (IL)
- Hebrew University of Jerusalem (IL)
- ORCID
- Venue
- Nature
- Published
- 2018-02-28
- Volume
- 555
- Issue
- 7695
- Pages
- 210-215
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2787902098
- Cited by
- 2,859
- References
- 111
- Citations by year
- 2026: 227 · 2025: 295 · 2024: 367 · 2023: 349 · 2022: 390 · 2021: 411 · 2020: 390 · 2019: 286 · 2018: 135
- FWCI
- 110.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Canadian Institute for Advanced Research
- Stiftelsen Kristian Gerhard Jebsen
- Wellcome Trust (085475, 076113)
- Rijksuniversiteit Groningen
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO SPI 92–266, NWO-VIDI 864.13.013, 864.13.013, 016.Vidi.178.056, SPI 92-266)
- Israel Science Foundation
- Abisch-Frenkel-Stiftung
- H2020 European Research Council (715772)
- FP7 Ideas: European Research Council (322698)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- gut microbiota, host genetics, genetic ancestry, environmental factors, diet, drugs, anthropometry, glucose, obesity
- MeSH terms
- Gastrointestinal Microbiome, Adolescent, Adult, Aged, Aged, 80 and over, Diet, Environment, Family Characteristics, Female, Glucose, Humans, Israel, Life Style, Male, Middle Aged, Obesity, Phenotype, RNA, Bacterial, RNA, Ribosomal, 16S, Twins, Reproducibility of Results, Cohort Studies, Twin Studies as Topic, Polymorphism, Single Nucleotide, Heredity, Young Adult, Gene-Environment Interaction, Healthy Volunteers
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