Genetic determinants of the gut microbiome in UK twins
Open accessAbstract
Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution.
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Twin studies and GWAS show that host genetics can influence the microbiome composition, and microbes can exert effects on the host genome, although the environment has an important role.
“Twin studies and GWAS show that host genetics can influence the microbiome composition, and microbes can exert effects on the host genome, although the environment has an important role [121,122].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [121]
The Introduction reports that twin studies found a small host-genetic effect while environmental factors were paramount in shaping the microbiome. The Discussion and Experimental Procedures describe associations between host genes and microbial taxa, including GWAS analyses. Our copy does not show that microbes exert effects on the host genome; its discussion of gene–microbe interactions does not establish that direction of effect. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHost genetics influence the gut microbiome, as shown by twin studies demonstrating shared community structures between related individuals and temporally stable heritable taxa.
“Host genetic influence15,16,1718, 19,20 on the gut microbiome is apparent from studies of monozygotic and dizygotic twin pairs that demonstrate shared community structures between related individuals21 and temporally stable heritable taxa17.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [17]
Christensenella spp. is associated with lean body mass and variants in genes such as ALDH1L1 and GNA12.
“For example, Christensenella spp. is associated with lean body mass and variants in genes such as ALDH1L1 and GNA12.65,66”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [66]
Genetics only perform a limited role in shaping the gut microbiota with an average level of 8.8% according to a 2016 data analysis of 1126 twins.
“Genetics only perform a limited role in shaping the gut microbiota with an average level of 8.8% according to a 2016 data analysis of 1126 twins [7].”
From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [7]
Host-genetic influences on gut microbiome composition are likely to play a role in influencing the rate and extent of microbial xenobiotic metabolism.
“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 Goodrich et al., 2016
Studies have found evidence for heritability of relative bacterial abundances or specific taxa.
“with studies finding evidence for heritability of relative bacterial abundances or specific taxa [15, 63–68]”
From Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana (2019) · cites this paper as [65]
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“Twin studies and GWAS show that host genetics can influence the microbiome composition, and microbes can exert effects on the host genome, although the environment has an important role (121,122).”
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The role of host molecules in communication with the resident and pathogenic microbiota: A review
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- Authors
- Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, M. A., Knight, R., Ober, C., Spector, T. D., Bell, J. T., Clark, A. G., & Ley, R. E.
- Affiliations
- Cornell University (US)
- King's College London (GB)
- University of California San Diego (US)
- University of Chicago (US)
- Corresponding author
- Ley, Ruth E.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 19
- Issue
- 5
- Pages
- 731-743
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4915943
- OpenAlex
- W2360231252
- Cited by
- 1,048
- References
- 92
- Citations by year
- 2026: 56 · 2025: 82 · 2024: 86 · 2023: 109 · 2022: 124 · 2021: 139 · 2020: 158 · 2019: 115 · 2018: 86 · 2017: 64 · 2016: 28 · 2015: 1
- FWCI
- 50.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Science Foundation
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0507-10228, NF-SI-0514-10027)
- King's College London
- National Institutes of Health (1dp2od007444-01)
- Medical Research Council (MR/N030125/1, MR/N01183X/1)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK109595, R01DK093595, P30DK020541)
- 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
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, host genetics, heritability, twins, Bifidobacterium, lactase gene, LCT gene, ALDH1L1, formate production, blood pressure, metabolism, olfaction, immune defense, self/non-self recognition, temporal stability
- MeSH terms
- Gastrointestinal Microbiome, Base Sequence, Female, United Kingdom, Humans, Male, Twins, Genetic Variation, Microbial Consortia
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