Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
Transl Stroke Res. 2023 Dec;14(6):811-828. doi: 10.1007/s12975-022-01096-3. Epub 2022 Oct 24.
Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS.
缺血性脑卒中（IS）仍然是全球范围内主要的致死和致残原因。几种机制，包括谷氨酸兴奋性毒性、钙超载、神经炎症、氧化应激、线粒体损伤和细胞凋亡，已知与 IS 的发病机制有关，但 IS 的潜在病理生理学机制尚未完全阐明。在过去的十年中，肠道微生物群被认为是直接或通过其代谢物影响宿主健康的关键调节剂。最近的研究表明，肠道细菌失调与高血压、糖尿病、肥胖、血脂异常和代谢综合征密切相关，这些都是心血管疾病的主要危险因素。越来越多的证据表明，IS 可导致肠道微生物群失调和肠道黏膜通透性增加，即“肠漏”，从而导致内毒素血症和细菌易位。反过来，肠道菌群失调和肠道通透性受损会改变肠道细菌代谢产物从肠道到大脑的信号特征。肠道微生物群衍生的产物和代谢物，如短链脂肪酸（SCFAs）、胆汁酸（BAs）、氧化三甲胺（TMAO）、脂多糖（LPS）和苯乙酰谷氨酰胺（PAGln），可以对包括大脑、肝脏和心脏在内的各种肠外器官产生有益或有害的影响。这些代谢物已被越来越多地认为是 IS 的生物标志物和介质。然而，肠道细菌代谢物在中风背景下的确切作用仍不完全清楚。对这些产物和代谢物的深入研究可能为 IS 的新型治疗方法的发展提供新的思路。
