Qian Xiao-Hang, Xie Ru-Yan, Liu Xiao-Li, Chen Sheng-di, Tang Hui-Dong
1Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
2Shanghai Guangci Memorial hospital, Shanghai 200025, China.
Aging Dis. 2022 Jul 11;13(4):1252-1266. doi: 10.14336/AD.2021.1215.
Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number of physiological and pathological processes in the human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that SCFAs are important mediators of gut-brain interactions and are involved in the occurrence and development of many neurodegenerative diseases, including Alzheimer's disease. This review summarizes the current research on the potential roles and mechanisms of SCFAs in AD. First, we introduce the metabolic distribution, specific receptors and signaling pathways of SCFAs in human body. The concentration levels of SCFAs in AD patient/animal models are then summarized. In addition, we illustrate the effects and mechanisms of SCFAs on the cognitive level, pathological features (Aβ and tau) and neuroinflammation in AD. Finally, we analyze the translational value of SCFAs as potential therapeutic targets for the treatment of AD.
短链脂肪酸(SCFAs)是膳食纤维经肠道微生物群发酵产生的重要代谢产物。SCFAs参与人体许多生理和病理过程,如宿主代谢、免疫调节、食欲调节。最近关于肠-脑相互作用的研究表明,SCFAs是肠-脑相互作用的重要介质,并参与包括阿尔茨海默病在内的许多神经退行性疾病的发生和发展。本综述总结了目前关于SCFAs在阿尔茨海默病中潜在作用和机制的研究。首先,我们介绍了SCFAs在人体中的代谢分布、特异性受体和信号通路。然后总结了阿尔茨海默病患者/动物模型中SCFAs的浓度水平。此外,我们阐述了SCFAs对阿尔茨海默病认知水平、病理特征(Aβ和tau)和神经炎症的影响及机制。最后,我们分析了SCFAs作为阿尔茨海默病潜在治疗靶点的转化价值。