Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Human Clinical Research Center for Cerebrovascular Disease, Changsha, China.
CNS Neurol Disord Drug Targets. 2024;23(1):102-121. doi: 10.2174/1871527322666230203140805.
The gut microbiome interacts with the brain bidirectionally through the microbiome-gutbrain axis, which plays a key role in regulating various nervous system pathophysiological processes. Trimethylamine N-oxide (TMAO) is produced by choline metabolism through intestinal microorganisms, which can cross the blood-brain barrier to act on the central nervous system. Previous studies have shown that elevated plasma TMAO concentrations increase the risk of major adverse cardiovascular events, but there are few studies on TMAO in cerebrovascular disease and vascular cognitive impairment. This review summarized a decade of research on the impact of TMAO on stroke and related cognitive impairment, with particular attention to the effects on vascular cognitive disorders. We demonstrated that TMAO has a marked impact on the occurrence, development, and prognosis of stroke by regulating cholesterol metabolism, foam cell formation, platelet hyperresponsiveness and thrombosis, and promoting inflammation and oxidative stress. TMAO can also influence the cognitive impairment caused by Alzheimer's disease and Parkinson's disease via inducing abnormal aggregation of key proteins, affecting inflammation and thrombosis. However, although clinical studies have confirmed the association between the microbiome-gut-brain axis and vascular cognitive impairment (cerebral small vessel disease and post-stroke cognitive impairment), the molecular mechanism of TMAO has not been clarified, and TMAO precursors seem to play the opposite role in the process of poststroke cognitive impairment. In addition, several studies have also reported the possible neuroprotective effects of TMAO. Existing therapies for these diseases targeted to regulate intestinal flora and its metabolites have shown good efficacy. TMAO is probably a new target for early prediction and treatment of stroke and vascular cognitive impairment.
肠道微生物组通过微生物-肠-脑轴与大脑双向相互作用，在调节各种神经系统生理病理过程中发挥关键作用。三甲胺 N-氧化物（TMAO）是通过肠道微生物代谢胆碱产生的，它可以穿过血脑屏障作用于中枢神经系统。先前的研究表明，血浆 TMAO 浓度升高会增加主要不良心血管事件的风险，但关于脑血管疾病和血管性认知障碍中 TMAO 的研究较少。本综述总结了十年来关于 TMAO 对中风和相关认知障碍影响的研究，特别关注其对血管性认知障碍的影响。我们表明，TMAO 通过调节胆固醇代谢、泡沫细胞形成、血小板高反应性和血栓形成以及促进炎症和氧化应激，对中风的发生、发展和预后有显著影响。TMAO 还可以通过诱导关键蛋白的异常聚集、影响炎症和血栓形成，影响阿尔茨海默病和帕金森病引起的认知障碍。然而，尽管临床研究已经证实了微生物-肠-脑轴与血管性认知障碍（脑小血管病和中风后认知障碍）之间的关联，但 TMAO 的分子机制尚未阐明，TMAO 的前体在中风后认知障碍过程中似乎起着相反的作用。此外，几项研究还报告了 TMAO 可能具有神经保护作用。针对调节肠道菌群及其代谢物的这些疾病的现有治疗方法已显示出良好的疗效。TMAO 可能是中风和血管性认知障碍早期预测和治疗的新靶点。
