Bacterial SNPs in the human gut microbiome associate with host BMI
Open accessAbstract
Genome-wide association studies (GWASs) have provided numerous associations between human single-nucleotide polymorphisms (SNPs) and health traits. Likewise, metagenome-wide association studies (MWASs) between bacterial SNPs and human traits can suggest mechanistic links, but very few such studies have been done thus far. In this study, we devised an MWAS framework to detect SNPs and associate them with host phenotypes systematically. We recruited and obtained gut metagenomic samples from a cohort of 7,190 healthy individuals and discovered 1,358 statistically significant associations between a bacterial SNP and host body mass index (BMI), from which we distilled 40 independent associations. Most of these associations were unexplained by diet, medications or physical exercise, and 17 replicated in a geographically independent cohort. We uncovered BMI-associated SNPs in 27 bacterial species, and 12 of them showed no association by standard relative abundance analysis. We revealed a BMI association of an SNP in a potentially inflammatory pathway of Bilophila wadsworthia as well as of a group of SNPs in a region coding for energy metabolism functions in a Faecalibacterium prausnitzii genome. Our results demonstrate the importance of considering nucleotide-level diversity in microbiome studies and pave the way toward improved understanding of interpersonal microbiome differences and their potential health implications.
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In a recent association study between bacterial SNVs and human BMI, most of the SNVs that could be replicated between Israeli and Dutch populations (15/17 SNV) belonged to Faecalibacterium and F. prausnitzii.
“In a recent association study between bacterial single-nucleotide variants (SNVs) and human BMI, the authors observed that most of the SNVs that could be replicated between Israeli and Dutch populations (15/17 SNV) belonged to Faecalibacte rium and F. prausnitzii . 23”
From Global genetic diversity of human gut microbiome species is related to geographic location and host health (2025) · cites this paper as [23]
The authors report high inflation in the quantile-quantile (Q-Q) plots obtained from F. prausnitzii associations, suggesting tight linkage of significant genetic variations associated with BMI.
“In the same vein, the authors report high inflation in the quantile-quantile (Q-Q) plots obtained from F. prausnitzii associations, suggesting tight linkage of sig nificant genetic variations associated with BMI.”
From Global genetic diversity of human gut microbiome species is related to geographic location and host health (2025) · cites this paper as [23]
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- Authors
- Zahavi, L., Lavon, A., Reicher, L., Shoer, S., Godneva, A., Leviatan, S., Rein, M., Weissbrod, O., Weinberger, A., & Segal, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Tel Aviv University (IL)
- Corresponding author
- Segal, Eran
- ORCID
- Venue
- Nature Medicine
- Published
- 2023-11
- Volume
- 29
- Issue
- 11
- Pages
- 2785-2792
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC10999242
- OpenAlex
- W4388216971
- Cited by
- 58
- References
- 47
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 16 · 2023: 1
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL160862)
- 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
- human gut microbiome, body mass index, metagenome-wide association study, host-microbe interactions, Bilophila wadsworthia, Faecalibacterium prausnitzii, energy metabolism, inflammation, microbial genetic diversity, obesity
- MeSH terms
- Gastrointestinal Microbiome, Bacteria, Humans, Body Mass Index, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Microbiota
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