Center for Applied Microbiome Sciences, The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA.
Gut Microbes. 2024 Jan-Dec;16(1):2371950. doi: 10.1080/19490976.2024.2371950. Epub 2024 Jul 15.
The gut microbial ecosystem communicates bidirectionally with the brain in what is known as the gut-microbiome-brain axis. Bidirectional signaling occurs through several pathways including signaling via the vagus nerve, circulation of microbial metabolites, and immune activation. Alterations in the gut microbiota are implicated in Alzheimer's disease (AD), a progressive neurodegenerative disease. Perturbations in gut microbial communities may affect pathways within the gut-microbiome-brain axis through altered production of microbial metabolites including ɣ-aminobutyric acid (GABA), the primary inhibitory mammalian neurotransmitter. GABA has been shown to act on gut integrity through modulation of gut mucins and tight junction proteins and may be involved in vagus nerve signal inhibition. The GABAergic signaling pathway has been shown to be dysregulated in AD, and may be responsive to interventions. Gut microbial production of GABA is of recent interest in neurological disorders, including AD. and Lactic Acid Bacteria (LAB), including , are predominant producers of GABA. This review highlights how temporal alterations in gut microbial communities associated with AD may affect the GABAergic signaling pathway, intestinal barrier integrity, and AD-associated inflammation.
肠道微生物生态系统与大脑之间存在双向交流，这种交流被称为肠道-微生物群-大脑轴。双向信号通过几种途径发生，包括通过迷走神经、微生物代谢物的循环和免疫激活进行信号传递。肠道微生物群的改变与阿尔茨海默病（AD）有关，AD 是一种进行性神经退行性疾病。肠道微生物群落的紊乱可能会通过改变包括γ-氨基丁酸（GABA）在内的微生物代谢物的产生来影响肠道-微生物群-大脑轴内的途径，GABA 是哺乳动物主要的抑制性神经递质。GABA 通过调节肠道粘蛋白和紧密连接蛋白来作用于肠道完整性，并且可能参与迷走神经信号抑制。在 AD 中，GABA 能信号通路已经被证明是失调的，并且可能对干预措施有反应。肠道微生物产生 GABA 是最近在神经紊乱疾病，包括 AD 中的研究热点。乳杆菌（LAB），包括 ，是 GABA 的主要产生菌。本综述强调了与 AD 相关的肠道微生物群落的时间变化如何影响 GABA 能信号通路、肠道屏障完整性和 AD 相关的炎症。
