肠道微生物组与阿尔茨海默病:已知与未知。

Gut microbiome and Alzheimer's disease: What we know and what remains to be explored.

机构信息

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

出版信息

Ageing Res Rev. 2024 Dec;102:102570. doi: 10.1016/j.arr.2024.102570. Epub 2024 Oct 30.

Abstract

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.

摘要

随着人类微生物组研究的进展,越来越多的科学证据证实了肠道微生物群在阿尔茨海默病发病机制中的关键作用。微生物组失调的特点是多样性和组成改变,以及病原体的增加,不仅影响各种肠道紊乱,还影响中枢神经系统紊乱,如 AD。基于过去几年积累的证据,现在很清楚的是,肠道微生物群可以通过肠-脑轴控制中枢神经系统(CNS)的功能,这为肠道和大脑之间的相互作用提供了新的视角。本综述的主要重点是肠道微生物群通过肠-脑轴与大脑之间相互作用的分子机制,以及肠道微生物群失调引发神经紊乱的发病和发展。由于微生物组失调,肠道和血脑屏障的通透性增加,这可能介导或影响 AD。与此同时,肠道微生物群的细菌种群可以大量分泌淀粉样蛋白和脂多糖,这可能会干扰与 AD 发病机制相关的信号通路和促炎细胞因子的形成。接下来对靶向肠道微生物群失调的潜在干预策略进行了批判性分析,包括使用益生菌、益生元、代谢物、饮食和粪便微生物移植。本综述的主要目的包括总结和讨论最近的发现,这些发现可能解释了肠道微生物群在 AD 发展中的作用。对这些基本机制的理解可能为 AD 的新型治疗策略提供新的思路。

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