Scientific Publications
A pomegranate polyphenol extract suppresses the microbial production of proatherogenic trimethylamine (TMA) in an in vitro human colon model
Molecular Nutrition and Food Research
High circulating levels of trimethylamineN-oxide (TMAO) correlate with metabolic diseases, predict adverse outcomes after heart failure and TMAO induce atherogenic effects in animal models and in human platelets. l-Carnitine and choline are major dietary precursors of TMAO. They are first converted to trimethylamine (TMA) by gut microbiota, which is absorbed by the host and converted to TMAO by hepatic monooxygenases. The minimal absorption of pomegranate polyphenols by the host suggests that they may reach the colon for further metabolism by the gut microbiome. Thus, we investigated the ability of a polyphenol-rich pomegranate extract to inhibit the production of TMA by human fecal microbiota. Batch fermentations were carried out (anaerobic, pH 6.7-7.1, 37°C) with 1% human fecal inoculum, l-carnitine or choline, and a polyphenol-rich pomegranate extract over 24-48 hours. Samples were collected over time and methylamines were quantified using LC-MS/MS with isotopically labelled internal standards. We show that the pomegranate extract delayed and reduced the rate of TMA production from both choline and l-carnitine. The extract had a dose-dependent effect on the metabolism of l-carnitine, with the highest dose delaying the average midpoint of the l-carnitine metabolism by 16 hours (95% CI = 8.4 to 24; p = 0.001) compared to the control. The pomegranate extract significantly reduced TMA production from choline and l-carnitine in vitro and should be assessed for its efficacy in vivo.
Molecular Nutrition and Food Research
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