Department of Neurology, Center for Memory and Aging, Alzheimer Disease Research Center, The University of New Mexico, Albuquerque, NM 87106, USA.
College of Medicine, The Ohio State University, Columbus, OH, USA 43210.
Neurosci Biobehav Rev. 2022 Oct;141:104814. doi: 10.1016/j.neubiorev.2022.104814. Epub 2022 Aug 4.
Structural and functional alterations to the gut microbiome, referred to as gut dysbiosis, have emerged as potential key mediators of neurodegeneration and Alzheimer disease (AD) pathogenesis through the "gut -brain" axis. Emerging data from animal and clinical studies support an important role for gut dysbiosis in mediating neuroinflammation, central and peripheral immune dysregulation, abnormal brain protein aggregation, and impaired intestinal and brain barrier permeability, leading to neuronal loss and cognitive impairment. Gut dysbiosis has also been shown to directly influence various mechanisms involved in neuronal growth and repair, synaptic plasticity, and memory and learning functions. Aging and lifestyle factors including diet, exercise, sleep, and stress influence AD risk through gut dysbiosis. Furthermore, AD is associated with characteristic gut microbial signatures which offer value as potential markers of disease severity and progression. Together, these findings suggest the presence of a complex bidirectional relationship between AD and the gut microbiome and highlight the utility of gut modulation strategies as potential preventative or therapeutic strategies in AD. We here review the current literature regarding the role of the gut-brain axis in AD pathogenesis and its potential role as a future therapeutic target in AD treatment and/or prevention.
肠道微生物组的结构和功能改变，称为肠道菌群失调，通过“肠-脑”轴，已成为神经退行性变和阿尔茨海默病（AD）发病机制的潜在关键介质。动物和临床研究的新数据支持肠道菌群失调在介导神经炎症、中枢和外周免疫失调、异常脑蛋白聚集以及肠道和大脑屏障通透性受损、导致神经元丧失和认知障碍方面的重要作用。肠道菌群失调也被证明直接影响参与神经元生长和修复、突触可塑性以及记忆和学习功能的各种机制。衰老和生活方式因素，包括饮食、运动、睡眠和压力，通过肠道菌群失调影响 AD 风险。此外，AD 与特征性的肠道微生物特征相关，这些特征为疾病严重程度和进展的潜在标志物提供了价值。总之，这些发现表明 AD 和肠道微生物组之间存在复杂的双向关系，并强调了肠道调节策略作为 AD 预防或治疗的潜在治疗靶点的效用。我们在这里回顾了关于肠道-大脑轴在 AD 发病机制中的作用及其作为 AD 治疗和/或预防未来治疗靶点的潜在作用的现有文献。
