Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation.

ABSTRACT: Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80-90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.

SUBMITTER: Iglesias-Carres L 

PROVIDER: S-EPMC8145906 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature