Dietary Polyphenols Inhibit Production of Trimethylamine, a Gut Microbial Metabolite Associated With Aging and Atherosclerosis

Andrew P NeilsonProf. Andrew P. Neilson, North Carolina State University, USA, will join the Polyphenols Applications 2023 congress and will present a talk entitled "Dietary Polyphenols Inhibit Production of Trimethylamine, a Gut Microbial Metabolite Associated With Aging and Atherosclerosis".

Cardiovascular disease causes ~32% of deaths worldwide. Elevated blood trimethylamine N-oxide (TMAO) levels were identified in 2011 as a risk factor for atherosclerosis development. TMAO is formed through a microbial-host axis involving oxidation of dietary choline to trimethylamine (TMA) by gut bacteria containing the cutC/D gene cluster. TMA is absorbed into circulation and oxidized to TMAO by hepatic flavin-containing monooxygenase 3. TMAO promotes cardiovascular disease through multiple mechanisms.

There is no FDA-approved drug to control TMAO levels, underscoring the need for complementary strategies to manage TMAO production. Dietary phytochemicals such as phenolics represent one potential solution. Phenolics have shown promise for altering the structure and function of the gut microbiome and providing cardioprotective benefits. Interest is emerging in TMAO-lowering activities of phenolics. There is a need to rapidly screen large numbers of phenolics and other dietary bioactives (compounds foods, extracts, etc.) to identify potential lead compounds for subsequent preclinical animal studies.

Prof. Neilson and his team developed and validated a high-throughput, low-volume 96-well ex vivo-in vitro anaerobic fecal fermentation method using human fecal samples and choline-d9 substrate and measuring the resultant TMA-d9. They paired this with a rapid, high-throughput analytical platform by employing an automated liquid handling robot for sample prep and a fast, sensitive 96-well LC-MS/MS method. Model validation experiments confirmed that choline-d9 utilization and TMA-d9 production occur with ~1:1 stoichiometry, with no background interference, and are dependent upon the presence of gut bacteria. Using this model, they identified chlorogenic acid, epicatechin and foods rich in these phenolics (coffee, cocoa and artichoke) as potent TMA production inhibitors.

In vitro and animal studies will elucidate the mechanisms of inhibition and demonstrate efficacy in vivo. TMA/TMAO-lowering activities may be a previously unknown mechanism by which dietary phenolics exert their cardioprotective effects.

Join us in Polyphenols Applications 2023 to learn more about Prof. Neilson's talk. 

Polyphenols Applications 2023 Congress
September 28-29, 2023 - Malta


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