Modulating the Microbiota-gut-brain Axis: A Promising Strategy for Alzheimer's Disease Prevention and Management

Alzheimer's disease (AD) is a progressive neurodegenerative disorder evident by cognitive decline and neuropathological hallmarks such as amyloid-β (Aβ) plaques and tau protein hyperphosphorylation. Recent evidence links gut microbiota dysbiosis to AD pathogenesis through the microbiota-gut-brain axis (MGBA), a complex bidirectional communication system entailing neural, immune, and metabolic pathways. This study aims to explore the mechanistic relationship between gut microbiota alterations and AD development and to assess the therapeutic potential of microbiota modulation through dietary, probiotic, and metabolite-based interventions. A thorough analysis was undertaken, blending evidence from preclinical animal models and clinical investigations. The effects of bacterial metabolites, microbial components (e.g., lipopolysaccharides, microbial amyloids), and interventions like probiotics, dietary fibers, and polyphenols were examined. Emphasis was placed on neuroinflammatory markers, Aβ deposition, blood-brain barrier integrity, and behavioral outcomes. Findings revealed that gut dysbiosis contributes to increased neuroinflammation, microglial activation, reduced short-chain fatty acid (SCFA) levels (especially butyrate), and compromised blood-brain barrier function. Bacterial LPS and amyloids may enhance Aβ aggregation and tau hyperphosphorylation. Probiotic supplementation and high-fiber/polyphenol-rich diets were noticed to restore microbial balance, increase SCFA production, attenuate Aβ deposition, and improve cognitive functions in animal models. Modulating gut microbiota shows potential as a complementary strategy for delaying or managing AD. Restoration of microbial equilibrium via dietary or probiotic approaches can mitigate neurodegeneration by targeting inflammation, microbial metabolite production, and immune responses. Further mechanistic studies and longitudinal human trials are needed to validate the clinical efficacy of MGBA-targeted therapies. Personalized microbiome-based interventions may pave the way for novel, non-invasive strategies to combat AD progression.