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.
A new manuscript fresh and hot on @biorxivpreprint. A really fun collab with @cdaili and multiple groups at @isbscience. Here we looked at how genetic variants and the composition of the microbiome explain the variation in human blood metabolites. https://t.co/NWS2iGUNVw
— Christian Diener (@thaasophobia) February 7, 2022