The Interplay of Inflammation and Gut-Microbiota Dysbiosis in Alzheimer's Disease: Mechanisms and Therapeutic Potential

炎症与肠道菌群失调在阿尔茨海默病中的相互作用:机制和治疗潜力

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Abstract

Alzheimer's disease (AD) represents a major global health challenge, characterised by progressive neurodegeneration that leads to cognitive decline. Inflammation is a key factor in the pathogenesis of AD, affecting both neuroinflammation and systemic inflammation. In AD, neuroinflammation is marked by the activation of microglia and the release of pro-inflammatory cytokines, which exacerbate neuronal damage and cognitive deficits. Systemic inflammation further compromises the blood-brain barrier (BBB), increasing its permeability and permitting the entry of inflammatory molecules and immune cells into the brain, thereby advancing the disease's hallmark features. Recent studies have elucidated the influence of gut microbiota dysbiosis on AD and inflammation. This imbalance is thought to be associated with alterations in the concentrations of short-chain fatty acids (SCFAs) and bile acids, which can modulate neuroinflammation and contribute to AD pathology. Additionally, imbalances in neurotransmitters resulting from gut microbiota dysbiosis can further disrupt brain function and facilitate AD progression. This review provides an overview of the hypothesis that systemic and central nervous system (CNS) inflammation, together with gut-microbiota dysbiosis, may interact to influence the development and progression of AD.

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