Modulating the Gut-Microbiota-Brain Axis in Alzheimer's Disease: Therapeutic Potential of Nutritional and Metabolic Factors.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia among the elderly, characterized by a gradual decline in memory and cognitive function. The growing body of evidence highlighting the interaction between the gut microbiota and the central nervous system has positioned the gut microbiota as a key area of research in AD pathogenesis. METHODS: This review critically evaluates the preclinical evidence and clinical trial outcomes, complemented by mechanistic studies and Mendelian randomization analyses, to assess the therapeutic potential of nutritional interventions targeting the gut-microbiota-brain axis in AD. RESULTS: Dietary components and patterns regulate the composition and function of the gut microbiota, which in turn influence brain function through the gut-microbiota-brain axis via chemical/metabolic, immune-mediated, and neural pathways. Specific nutrients, microbial metabolites, and dietary patterns have been shown to exert either protective or detrimental effects on AD pathology and cognitive function. Emerging strategies, including precision nutrition, fecal microbiota transplantation, and next-generation microbiome-based therapies, offer new avenues for AD prevention and treatment. CONCLUSIONS: Nutritional interventions targeting the gut-microbiota-brain axis represent a promising approach for the comprehensive prevention and management of AD. Further mechanistic and clinical studies are warranted to translate these findings into effective therapeutic strategies.