Introduction: Plasma levels of trimethylamine oxide (TMAO), a metabolite of TMA which is exclusively produced from choline, l-carnitine and betaine by the gut microbiota, has been shown to predict the risk of death from heart failure [1]. Plasma TMAO has also been reported to correlate with a range of non-communicable diseases such as cardiovascular disease (CVD), diabetes and neurodegenerative diseases which pose serious health, social and economic burdens worldwide [2, 3]. However, there are no current sustainable treatments to reduce TMAO levels in those at risk. Polyphenol-rich diets have been shown to protect against metabolic diseases such as CVD [4]. Aims and methodology: We investigated the potential and the capacity to which foods rich in polyphenols can alter TMA production from choline and betaine using the in-vitro batch fermentation human colon model [5], followed by metabolite analysis using LC-MS. We tested a black rice (BR) anthocyanin extract, an ellagitannin-rich pomegranate peel extract (DermogranateTM) and purified resveratrol. A written informed consent was obtained from all participating subjects, the trial is registered at http:// www. Clinical trials. gov (NCT02653001) and the study was approved by the London—Westminster Research Ethics Committee (15/LO/2169) and the Quadram Institute Bioscience (Human Research Governance committee (IFR01/2015). Results: We demonstrate that BR anthocyanins (predominantly cyanidin-3-Glc) reduced TMA production from choline by 22% in a manner that is consistent with inhibition of the choline TMA-lyase pathway (F (1645, 1158) = 487.4, P< 0.05, N = 5). The Dermogranate®, which contains mainly ellagitannins including β-punicalagin, reduced TMA production from choline in a manner consistent with the inhibition of both the TMA lyase (F (914.7, 886.6) = 193.2, P < 0.0001, N = 4) and the betaine reductase pathway (F (173.5, 409.1) = 235.5, P < 0.001, N=4). We substantiated this notion by showing inhibition of betaine metabolism in the presence of choline and a lack of betaine production from choline in experiments in which no betaine was supplemented. DermogranateTM treatment also increased the production of lactic acid, suggesting a prebiotic activity (F (2.1, 15.36) = 13.26, P < 0.05, N=4). Resveratrol had no significant effect on TMA production from choline. Conclusion: We have demonstrated the potential for BR and DermogranateTM to be developed as functional foods that may be of benefit to people who have a high capacity to produce TMA/TMAO and are therefore at greater risk of developing chronic diseases or of extreme events after heart failure. The DermogranateTM may also have prebiotic activity.
Physiology 2021 (2021) Proc Physiol Soc 48, PC060
Poster Communications: The modification of choline and betaine metabolism to TMA by the gut microbiota using polyphenol rich foods
Priscilla Day-Walsh1, Emad Shehata1, 2, Lee Kellingray1, Arjan Narbad1, Salvatore Rapisarda3, Paul Kroon1
1 Food Innovation & Health, Quadram Institute Bioscience, Norwich, United Kingdom 2 National Research Centre, 33 El Buhouth St., Dokki, 12622, Cairo, Egypt 3 Medinutrex - Mediterranean Nutraceutical Extracts srls, via Vincenzo Giuffrida, 202, , 95128 Catania, Italy
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Where applicable, experiments conform with Society ethical requirements.