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The gut–brain axis in Alzheimer’s disease: how gut microbiota modulate microglial function

Huan Wang, Feifan Yang, Zhejianyi Gao, Ze-Dong Cheng, Xicai Liang

2025Frontiers in Aging9 citationsDOIOpen Access PDF

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder that can be caused by multiple factors, such as abnormal amyloid-beta (Aβ) deposition, pathological changes in Tau protein, lipid metabolism disorders, and oxidative stress. Recent studies have revealed the potential link between gut microbiota and AD, particularly the impact of gut microbiota and its derivatives on microglia. As immune cells in the central nervous system (CNS), microglia are involved in neuroinflammation and the regulation of cognitive function. Research indicates that the dysregulation of gut microbiota may affect the phenotype and function of microglia through various mechanisms, including direct metabolite action and indirect immune and neurotransmitter regulation. This article reviews the direct and indirect effects of gut microbiota and its derivatives on microglia, explores their role in the pathogenesis of AD, and discusses therapeutic strategies based on gut microbiota, such as dietary regulation, probiotics, fecal microbiota transplantation, and traditional Chinese medicine. Although existing studies have shown the potential of these interventions, further research is needed to completely understand their application in the treatment of AD.

Topics & Concepts

Gut floraNeuroinflammationMicrogliaImmune systemGut–brain axisBiologyPathogenesisFunction (biology)Central nervous systemImmunologyNeuroscienceNeurotransmitterDiseasePhenotypeInflammationInnate immune systemMetaboliteCell biologyImmunityPathologicalLipid metabolismNervous systemHuman studiesEnteric nervous systemDysbiosisOxidative stressMultiple sclerosisGut bacteriaGut microbiota and healthNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments
The gut–brain axis in Alzheimer’s disease: how gut microbiota modulate microglial function | Litcius