氧化三甲胺与心房颤动相关的研究进展

Research progress on the relationship between trimethylamine oxide and atrial fibrillation

肠道菌群是一个复杂的群落,它与宿主的动态功能相互作用,适当的肠道微生物群结构和代谢物功能对于维持体内平衡至关重要。近些年,大量研究证明肠道菌群及其衍生代谢物影响着心血管疾病的发生发展,其中就包括心律失常,而心房颤动是最常见的心律失常之一。氧化三甲胺(TMAO)是目前研究最多的肠道菌群衍生代谢物之一,研究发现TMAO与心房颤动的发生发展密切相关。很多流行病学研究表明,TMAO在心房颤动的发生、发展及预后中发挥作用。TMAO通过促进多种心血管危险因素的发生来增加心房颤动易感性。此外,TMAO还可通过激发炎症反应、致使心脏纤维化与心房焦亡来促进心房结构的重构,其水平升高还可增加心房电生理不稳定性,引发异位活动致电生理重构,亦可直接或间接激活自主神经系统引起神经重塑而诱发心房颤动。另外,TMAO水平升高可诱导血小板高反应性,从而促进动脉血栓形成提高心房颤动血栓栓塞发生率,并且与消融术后心房颤动复发也明显相关。研究发现,TMAO在心房颤动防治方面有着一定的潜在价值。在饮食习惯上可以通过减少摄入生成三甲胺的膳食前体从而减少循环中TMAO水平、通过某些药物增加TMAO从肾脏的排泄以及直接服用益生元、益生菌或通过粪便菌群移植的方法调节肠道菌群构成,进而改变肠道菌群衍生代谢物水平。本文根据相关文献的研究结果从上述方面进行综述,以期为今后的相关研究提供一定的理论依据。

The gut microbiota is a complex community that interacts with the dynamic functions of the host,and proper gut microbiota structure and metabolite function are essential for maintaining homeostasis.In recent years,a large number of studies have demonstrated that the gut microbiota and its derived metabolites influence the development of cardiovascular diseases,including cardiac arrhythmias,of which atrial fibrillation is one of the most common.Trimethylamine oxide(TMAO)is one of the most studied gut microbiota-derived metabolites,and TMAO has been found to be strongly associated with the development of atrial fibrillation.Many epidemiological studies have shown that TMAO plays a role in the onset,development and prognosis of atrial fibrillation(AF).TMAO increases the susceptibility to AF by contributing to the development of multiple cardiovascular risk factors.In addition,TMAO promotes atrial structural remodeling by stimulating inflammatory responses,causing cardiac fibrosis and atrial pyroptosis.Elevated levels of TMAO also increase atrial electrophysiological instability,triggering ectopic activity that leads to electrophysiological remodeling,and directly or indirectly activate the autonomic nervous system to cause neural remodeling that induces atrial fibrillation.In addition,elevated levels of TMAO induce platelet hyper-reactivity,which promotes arterial thrombosis,increases the incidence of thromboembolism in AF,and is also significantly associated with AF recurrence after ablation.TMAO has been shown to have some potential values in the prevention and treatment of AF.The composition of the gut microbiota can be modulated through dietary habits by reducing the intake of trimethylamine-producing dietary precursors and thereby reducing circulating levels of TMAO,by increasing the excretion of TMAO from the kidneys through certain drugs,and by directly taking prebiotics,probiotics,or through fecal flora transplantation,which can in turn alter the levels of gut microbiota-derived metabolites.In this paper,we review the above aspects based on the findings of the related literature,with the aim of providing a theoretical basis for future related studies.