Evaluation of the effects of red wine on the gut flora and production of trimethylamine-N-oxide (TMAO)

Abstract

Evaluation of the effects of red wine on the gut flora and production of trimethylamine-N-oxide (TMAO)Background: - Recent evidences indicate that trimethylamine-N-oxide (TMAO) is a pro-atherosclerotic metabolite, dependent of dietary phosphatidylcholine and intestinal flora. Carnitine and phosphatidylcholine (lecithin) derivatives are the main dietary sources, mostly from eggs, red meat, liver and pork. Intestinal flora pattern favoring TMAO formation is very similar to that predisposing to insulin resistance and obesity: an increased Firmicutese phylum ratio over Bacteirodetes phylum. Gut microbiota is sensitive and adaptable; the use of prebiotics and probiotics can change the Firmicutes / Bacteroidetes ratio. Red wine (RW) polyphenols content and its possible antimicrobial effect could play an effect in the gut flora modification and promote beneficial bacteria proliferation. However, the influence of RW upon TMAO is unknown. Hence, the aim of this study is to investigate the effects of RW upon intestinal flora and plasma TMAO concentration.Methods: It is a prospective, crossover, randomized, controlled interventional study, with patients from Instituto do Coração (InCor), FMUSP. Forty-two men with diagnosed atherosclerotic disease will be studied: each subject subject will be randomly assigned to receive both treatments, intervention and control. In the intervention period, patients will receive 250 mL / day of red wine per Day, 5 days a week, for 3 weeks. Patients will follow their usual diet without prebiotics, probiotics and other poliphenolics sources. At the end of each stage, plasma levels of TMAO and intestinal microbiota will be evaluated.Gut flora will be idientified by 16S ribosomal RNA (rNA) gene sequencing. The determination of TMAO in plasma will be performed by liquid chromatography coupled to mass spectrometry.Expected Results:We expect to determine whether the RW acts upon the intestinal flora and whether it influences plasma concentration of TMAO. The study will also provide new understanding of the possible beneficial effect of RW in men. (AU)