Genome–microbiome interplay provides insight into the determinants of the human blood metabolome
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Abstract
Variation in the blood metabolome is intimately related to human health. However, few details are known about the interplay between genetics and the microbiome in explaining this variation on a metabolite-by-metabolite level. Here, we perform analyses of variance for each of 930 blood metabolites robustly detected across a cohort of 1,569 individuals with paired genomic and microbiome data while controlling for a number of relevant covariates. We find that 595 (64%) of these blood metabolites are significantly associated with either host genetics or the gut microbiome, with 69% of these associations driven solely by the microbiome, 15% driven solely by genetics and 16% under hybrid genome-microbiome control. Additionally, interaction effects, where a metabolite-microbe association is specific to a particular genetic background, are quite common, albeit with modest effect sizes. This knowledge will help to guide targeted interventions designed to alter the composition of the human blood metabolome.
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The human gut microbiome is a major determinant of plasma metabolome, potentially playing a more dominant role than genetics.
“The rationale is further supported by several studies that demonstrated that the human gut microbiome is a major determinant of plasma metabolome, potentially playing a more dominant role than genetics.26–28”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [28]
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- Authors
- Diener, C., Dai, C. L., Wilmanski, T., Baloni, P., Smith, B., Rappaport, N., Hood, L., Magis, A. T., & Gibbons, S. M.
- Affiliations
- Institute for Systems Biology (US)
- University of Washington (US)
- Corresponding author
- Magis, Andrew T.
- Gibbons, Sean M.
- ORCID
- Venue
- Nature Metabolism
- Published
- 2022-11-10
- Volume
- 4
- Issue
- 11
- Pages
- 1560-1572
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC9691620
- OpenAlex
- W4308772947
- Cited by
- 102
- References
- 82
- Citations by year
- 2026: 18 · 2025: 33 · 2024: 29 · 2023: 20 · 2022: 2
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R01DK133468)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- blood metabolome, gut microbiota, host genetics, metabolomics
- MeSH terms
- Feces, Humans, RNA, Ribosomal, 16S, Metabolomics, Metabolome, Microbiota
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