Cited by 102Gut microbiota and healthMetabolomics and Mass Spectrometry StudiesNutrition, Genetics, and Disease

Genome–microbiome interplay provides insight into the determinants of the human blood metabolome

Open access
Diener, Christian, Dai, Chengzhen L., Wilmanski, Tomasz, Baloni, Priyanka, Smith, Brett, Rappaport, Noa, Hood, Leroy, Magis, Andrew T. +1 more·2022·Nature Metabolism

Published version of a preprint

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”

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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.
Venue
Nature Metabolism
Published
2022-11-10
Volume
4
Issue
11
Pages
1560-1572
ISSN
2522-5812 (ISSN-L)
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
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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