Mechanisms and Therapeutic Targeting of the GutMicrobiota-Immune-Brain Axis in Alzheimer’s Disease

BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease globally. The main pathological features of AD are amyloid-β (Aβ) deposition and tau hyperphosphorylation. Recent studies suggest that the gut microbiota-immunity-brain axis plays an important role in the onset and progression of AD. Gut microbiota dysbiosis may impair intestinal barrier integrity and promote the entry of pro-inflammatory mediators into the circulation. Pro-inflammatory signals in the bloodstream may further activate the central immune system, drive microglial polarization, and increase the release of inflammatory factors in the brain. The resulting neuroinflammatory cascade may aggravate Aβ accumulation, tau phosphorylation, and cognitive impairment, although this mechanism has not been conclusively established in humans. METHODS AND RESULTS: Based on relevant literature on AD, gut microbiota, immunity, neuroinflammation, and the gut-brain axis, this article systematically reviews the mechanism of action of the microbiota-immunity-brain axis in AD. Current intervention strategies targeting this axis, including probiotics, fecal microbiota transplantation, dietary interventions, and traditional Chinese medicine, were also discussed. Such intervention measures have the potential to regulate the balance of the gut microbiota, reduce neuroinflammation, and slow the progression of AD pathology. CONCLUSION: It is essential to integrate multi-omics approaches in future research to deepen the understanding of AD pathogenesis and support the development of more precise and personalized treatment strategies.