ABSTRATC

In recent years, emerging studies have observed gut microbiota (GM) alterations in Alzheimer’s disease (AD), even in individuals with mild cognitive impairment (MCI). Further, impaired sleep and circadian patterns are common symptoms of AD, while sleep and circadian rhythm disruption (SCRD) is associated with greater β-amyloid (Aβ) burden and AD risk, sometimes years before the clinical onset of AD. Moreover, reports have demonstrated that GM and its metabolites exhibit diurnal rhythmicity and the role of SCRD in dampening the GM rhythmicity and eubiosis. This review will provide an evaluation of clinical and animal studies describing GM alterations in distinct conditions, including AD, sleep and circadian disruption. It aims to identify the overlapping and distinctive GM alterations in these conditions and their contributions to pathophysiology. Although most studies are observational and use different methodologies, data indicate partial commonalities in GM alterations and unanimity at functional level. Finally, we discuss the possible interactions between SCRD and GM in AD pathogenesis, as well as several methodological improvements that are necessary for future research.

文摘

近年来，新兴研究已经观察到阿尔茨海默病 (AD) 中肠道微生物群 (GM) 的改变，甚至在轻度认知障碍 (MCI) 的个体中也是如此。此外，睡眠障碍和昼夜节律模式是 AD 的常见症状，而睡眠和昼夜节律紊乱 (SCRD) 与更大的 β-淀粉样蛋白 (Aβ) 负担和 AD 风险相关，有时在 AD 临床发病前数年。此外，报告表明 GM 及其代谢物表现出昼夜节律性和 SCRD 在抑制 GM 节律性和优生化方面的作用。本综述将对描述不同条件下 GM 改变的临床和动物研究进行评估，包括 AD、睡眠和昼夜节律紊乱。它旨在确定这些条件中重叠和独特的 GM 改变及其对病理生理学的贡献。尽管大多数研究是观察性的并使用不同的方法，但数据表明 GM 改变的部分共性和功能水平的一致性。最后，我们讨论了 AD 发病机制中 SCRD 和 GM 之间可能的相互作用，以及未来研究所需的几种方法学改进。