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

Nat Metab. 2022 Nov;4(11):1560-1572. doi: 10.1038/s42255-022-00670-1. Epub 2022 Nov 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Feces
  • Humans
  • Metabolome / genetics
  • Metabolomics*
  • Microbiota*
  • RNA, Ribosomal, 16S / genetics


  • RNA, Ribosomal, 16S