Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe –/– mice through different mechanisms

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe –/– mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe–/– mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

氧化三甲胺（Trimethylamine N-oxide, TMAO）是一种依赖肠道菌群的代谢产物，已被证实可加重心血管疾病。然而，TMAO参与心血管疾病进展的具体机制尚未阐明。本研究旨在探讨TMAO对动脉粥样硬化（atherosclerosis, AS）发生发展的影响及其潜在作用机制。我们将载脂蛋白E敲除（Apoe–/–）小鼠分为四组，分别在正常饮食与西式饮食中添加胆碱或TMAO，持续干预12周。结果显示，无论正常饮食还是西式饮食组，补充胆碱或TMAO均显著加速了Apoe–/–小鼠的动脉粥样硬化斑块进展。此外，补充胆碱或TMAO可升高小鼠血清血脂水平，并增强主动脉根部的炎症应答。尤为值得注意的是，西式饮食联合胆碱或TMAO补充可改变小鼠肠道菌群组成与胆汁酸代谢谱。综上，在西式饮食喂养的小鼠中，胆碱或TMAO或可通过调控肠道菌群促进动脉粥样硬化；而在正常饮食喂养的小鼠中，则可能通过其他途径发挥促动脉粥样硬化作用，即便仅在正常饮食中补充胆碱或TMAO，仍可促进动脉粥样硬化的发生发展。