从肠道菌群角度认识阿尔茨海默病的潜在发病机制

过去10年中，人们逐渐认识到肠道微生物群的多样性及菌群平衡在维护宿主健康中发挥的作用。肠道微生物及其代谢产物通过一系列的生化、免疫和生理功能环节与宿主进行交流，从而影响宿主的稳态和健康。阿尔茨海默病(Alzheimer’s disease，AD)是一种复杂的神经退行性疾病，其易感性和发展过程受年龄、遗传和表观遗传等因素的影响。研究发现，肠道微生物群的紊乱(组成改变和易位)与神经系统疾病(AD)有关，胃肠道通过肠脑轴与中枢神经系统进行沟通，包括对神经的直接作用、内分泌途径和免疫调控方式。动物模型、粪便菌群移植及益生菌干预为肠道菌群与AD的相关性提供了证据。外漏的细菌代谢产物可能直接损害神经元功能，也可能诱发神经炎症，促进AD的发病。本文主要综述了肠道微生物群与AD的关联和作用机制，以期为通过改善肠道菌群结构预防AD的可能干预措施提供依据。

Understanding the underlying pathogenesis of Alzheimer’s disease from the perspective of gut microbiota

In the past decade, it has been realized that the diversity and balance of the gut microbiota plays a critical role for health. Gut microbiota and their metabolites interact with the host through a series of biochemical, immunological and physiological processes to affect the homeostasis and health of the host. Many studies have been reported that the disorders of the gut microbiota are associated with neurological diseases. Alzheimer’s disease (AD) is a complex neurodegenerative disease, its susceptibility and development are influenced by age, heredity and epigenetic factors. New evidence suggested that the composition change and translocation of the gut microbiota were associated with the development of AD, but its causal relationship and possible mechanisms need to be explored. Communications between the central nervous system and the gut axis relied mainly on three manners, including direct neural communication, endocrine pathways and immune regulation. Evidence from animal models of fecal microbiota transplantation and probiotic intervention suggested the association of gut microbiota with AD. Exogenous bacterial metabolites can directly impair neuronal function, and induce neuroinflammation to promote the onset of AD. In this review, we focused on the relationship and possible mechanisms of gut microbiota with AD, and provided evidence for possible interventions to prevent AD by improving the structure of gut microbiota.