Potential of phenolic compounds and their gut microbiota-derived metabolites to reduce microbial TMA formation: Application of an in vitro fermentation high throughput screening model

Trimethylamine N-oxide (TMAO) is a pro-atherosclerotic product of dietary choline metabolism generated by a microbiome-host axis. The first step in this pathway is enzymatic metabolism of choline to trimethylamine (TMA) by the gut microbiota. This reaction could be targeted to reduce atherosclerosis risk. We aimed to evaluate potential inhibitory effects of select dietary phenolics and their relevant gut microbial metabolites on TMA production via a human ex vivo-in vitro fermentation model. Various phenolics inhibited choline use and TMA production, especially larger compounds or their larger metabolites, without altering cell respiration or cell growth. However, inhibitory effects decreased at late fermentation times, which suggest that these compounds delay choline metabolism rather than completely inhibiting TMA formation. Overall, caffeic acid, catechin and epicatechin were the most effective non-cytotoxic inhibitors of choline use and TMA production. Thus, these compounds are proposed as lead bioactives to test in vivo.