Diet-gut microbiota-immune-brain interactions in aging: mechanistic pathways and clinical implications

With rising life expectancy and global population aging, cognitive decline has become a major and growing public health challenge. Advances in nutritional neuroscience highlight the gut microbiota-immune-brain axis as a key biological pathway through which diet may influence cognitive function during aging. The gut microbiota, a metabolically active ecosystem, responds dynamically to habitual dietary patterns and produces bioactive metabolites capable of modulating immune signaling, neuroinflammation, and neuronal function. Diets rich in microbiota-modulating foods (e.g., dietary fiber, polyphenols, prebiotics, and probiotics) promote beneficial microbial communities. These communities support short-chain fatty acid production, maintain intestinal barrier integrity, and regulate systemic immune responses, processes increasingly associated with cognitive resilience in aging populations. In contrast, Western-style dietary patterns characterized by high intakes of saturated fats and refined sugars are linked to microbial dysbiosis, impaired gut barrier function, metabolic endotoxemia, and chronic low-grade inflammation, which may contribute to neuroinflammatory pathways involved in cognitive decline. This narrative review synthesizes evidence from observational studies, dietary intervention trials, and mechanistic animal models to examine how diet-driven alterations in gut microbiota composition and microbial metabolites interact with and modulate immune pathways to influence brain function in aging populations. Although emerging evidence supports the biological plausibility of this axis in cognitive health, current evidence remains constrained by methodological heterogeneity, short intervention durations, limited functional insight, and substantial inter-individual variability in microbiota responsiveness. In particular, much of the mechanistic understanding derives from preclinical research, while human evidence remains largely associative and insufficient to establish causal pathways. Future research should integrate longitudinal cohort designs, harmonized cognitive assessment tools, and repeated profiling of microbial and host metabolites to clarify the functional and causal links between diet, microbial metabolism, immune regulation, and brain aging. A more integrated understanding of these interactions may help inform targeted, microbiome-informed nutritional strategies for supporting healthy cognitive aging, while maintaining appropriate caution in clinical interpretation.