4.7 Article

Potential of Phenolic Compounds and Their Gut Microbiota-Derived Metabolites to Reduce TMA Formation: Application of an In Vitro Fermentation High-Throughput Screening Model

Journal

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 70, Issue 10, Pages 3207-3218

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.2c00247

Keywords

atherosclerosis; food bioactives; gut microbiota metabolites; phenolic compounds; TMA

Funding

  1. Plants for Human Health Institute North Carolina State University
  2. North Caroline Agricultural Research Service (NCARS)
  3. Hatch Program of the National Institute of Food and Agriculture (NIFA), U.S. Department of Agriculture

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In this study, it was found that phenolic compounds such as caffeic acid, catechin, and epicatechin could effectively inhibit the production of TMA, suggesting their potential as lead bioactives for in vivo testing.
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 the 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. The most bioactive compounds tested (caffeic acid, catechin, and epicatechin) reduced TMA-d(9) formation (compared to control) by 57.5 +/- 1.3 to 72.5 +/- 0.4% at 8 h and preserved remaining choline-d(9) concentrations by 194.1 +/- 6.4 to 256.1 +/- 6.3% at 8 h. These inhibitory effects were achieved without altering cell respiration or cell growth. However, inhibitory effects decreased at late fermentation times, which suggested that these compounds delay choline metabolism rather than completely inhibiting TMA formation. Overall, caffeic acid, catechin, and epicatechin were the most effective noncytotoxic inhibitors of choline use and TMA production. Thus, these compounds are proposed as lead bioactives to test in vivo.

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