Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.

ABSTRACT: The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs

SUBMITTER: Andrikopoulos P 

PROVIDER: S-EPMC10511707 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature