Carnitine, a dietary quaternary amine mainly from red meat, is metabolized to trimethylamine (TMA) by gut microbiota and subsequently oxidized to trimethylamine-N-oxide (TMAO) by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of flavonoids from oolong tea and citrus peels on reducing TMAO formation and protecting vascular inflammation in carnitine-feeding mice. The results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group, whereas the plasma TMAO was remarkedly reduced by flavonoids used. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, oolong tea extract decreased mRNA levels of vascular inflammatory markers such as tissue necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Polymethoxyflavones significantly lowered the expression of VCAM-1 and showed a decreasing trend in TNF-α and E-selectin mRNA expression compared to the carnitine group. Genus-level analysis of the gut microbiota in the cecum showed that these dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to the carnitine only group. Administration of polymethoxyflavones increased Akkermansia in mice.
Keywords: atherosclerosis; carnitine; dietary phenolic compounds; flavin monooxygenases (FMOs); gut microbiota; trimethylamine--oxide (TMAO).