Scientific Publications
Punicalagin is the Key Pomegranate Polyphenol Inhibiting Gut Microbial Trimethylamine (TMA) Production from l-Carnitine
Food & Function, 17(4), 1827-1840
TMAO has been linked to various cardiometabolic diseases and all-cause mortality risk. A major dietary precursor of TMAO is l-carnitine. l-Carnitine is metabolised by microbiota to ?-butyrobetaine (?-BB), followed by trimethylamine (TMA), and is then oxidised to TMAO in the liver. Previously, we have shown that a polyphenol-rich pomegranate extract dose-dependently inhibited the production of ?-BB and TMA from l-carnitine. Here, we further investigated the effects of the pomegranate extract and its individual constituents/metabolites (polyphenols, spray-drying agent gum Arabic, and urolithins) on the microbial metabolism of l-carnitine to ?-BB and TMA using a high-throughput in vitro model of the human colon. A small-scale, high-throughput colon model was inoculated with l-carnitine, individual constituents of the extract (2 mg/mL), and 1% human faecal inoculum, while continuously monitoring pH. Samples were collected over 48 hours, and methylamines were quantified using LC-MS/MS with isotopically labelled internal standards. Punicalagin, but not the other constituents, inhibited the conversion of l-carnitine to ?-BB (p < 0.001) and almost completely blocked TMA production compared to the control (p < 0.003). Furthermore, including the whole pomegranate extract in the high-throughput colon model significantly reduced the pH and completely inhibited l-carnitine metabolism, suggesting that acidification may also inhibit microbial l-carnitine metabolism. Here it was shown that, of all the tested phenolic and non-phenolic components of the pomegranate extract, only punicalagin inhibited TMA production from l-carnitine, highlighting it as a promising inhibitor of TMA and potentially TMAO formation.
Food & Function, 17(4), 1827-1840
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