Gut Microbiota Disorder, Gut Epithelial and Blood-Brain Barrier Dysfunctions in Etiopathogenesis of Dementia: Molecular Mechanisms and Signaling Pathways.

肠道微生物紊乱，肠道上皮和血脑屏障功能障碍在痴呆发病机制中的作用：分子机制和信号通路

Abstract

Emerging evidences indicate a critical role of the gut microbiota in etiopathogenesis of dementia, a debilitating multifactorial disorder characterized by progressive deterioration of cognition and behavior that interferes with the social and professional functions of the sufferer. Available data suggest that gut microbiota disorder that triggers development of dementia is characterized by substantial reduction in specific species belonging to the Firmicutes and Bacteroidetes phyla and presence of pathogenic species, predominantly, pro-inflammatory bacteria of the Proteobacteria phylum.

新出现的证据表明肠道微生物群在痴呆症的发病机制中起着关键作用，痴呆是一种使人衰弱的多因素引起的疾病，其特征是认知和行为的进行性恶化，对患者的社会和职业功能造成干扰。现有数据表明，引发痴呆发展的肠道微生物群紊乱的特征在于厚壁菌属和拟杆菌属的特定物种的显著减少以及致病物种（主要是变形菌门的促炎细菌）的存在。

These changes in gut microbiota microecology promote the production of toxic metabolites and pro-inflammatory cytokines, and reduction in beneficial substances such as short chain fatty acids and other anti-inflammatory factors, thereby, enhancing destruction of the gut epithelial barrier with concomitant activation of local and distant immune cells as well as dysregulation of enteric neurons and glia. This subsequently leads to blood-brain barrier dysfunctions that trigger neuroinflammatory reactions and predisposes to apoptotic neuronal and glial cell death, particularly in the hippocampus and cerebral cortex, which underlie the development of dementia.

这些肠道微生物群微生态学变化促进了有毒代谢物和促炎细胞因子的产生，以及有益物质如短链脂肪酸和其他抗炎因子的减少，从而加重了肠上皮屏障的破坏，伴随着局部刺激和远端免疫细胞以及肠神经元和神经胶质细胞的失调，这随后引发血脑屏障功能障碍，从而引发神经炎症反应并易于引起凋亡神经元和神经胶质细胞死亡，特别是在海马和大脑皮质中的神经元和细胞，这是引发痴呆的基础。

However, the molecular switches that control these processes in the histo-hematic barriers of the gut and brain are not exactly known. This review integrates very recent data on the molecular mechanisms that link gut microbiota disorder to gut epithelial and blood-brain barrier dysfunctions, underlying the development of dementia. The signaling pathways that link gut microbiota disorder with impairment in cognition and behavior are also discussed. The review also highlights potential therapeutic options for dementia.

然而，在肠道和大脑的组织-血管屏障中控制这些过程的分子机制仍尚不完全清楚。该综述收集了最新的数据，这些数据将肠道微生物群病症与肠道上皮和血脑屏障功能障碍——痴呆症发展的基础联系起来。本文还讨论了将肠道微生物群紊乱与认知和行为损害联系起来的信号通路。同时强调了痴呆症的潜在治疗选择。

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