Gut Microbiome-Mediated Neuroprotective Effect of the Mediterranean Diet: A Narrative Review of Cognitive Aging, Alzheimer's Disease, and Parkinson's Disease.

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are major neurodegenerative disorders for which disease-modifying therapies are limited. Increasingly, evidence suggests that diet influences neurodegenerative risk through interactions among the gut microbiome, immune system, and brain. The Mediterranean diet (MD) is associated with improved cognitive health, but the mechanisms underlying its potential neuroprotective effects remain incompletely understood. Objective: In this narrative review, evidence on microbiome-mediated mechanisms linking MD adherence to neuroprotection was synthesized, and how Mediterranean dietary components influence microbial ecology, metabolites, immune regulation, and neuroinflammation relevant to cognitive aging, AD, and PD was evaluated. Methods: Evidence from experimental, observational, and clinical studies was reviewed, focusing on microbial metabolites, intestinal barrier integrity, immune regulation, and inflammatory pathways. Discussion: Mediterranean dietary components, including fiber, polyphenols, whole grains, legumes, nuts, extra-virgin olive oil, and omega-3 fatty acids, may promote beneficial microbial communities and metabolite production. Short-chain fatty acids, secondary bile acids, indole derivatives, and phenolic metabolites may strengthen the intestinal and blood-brain barriers, regulate immune responses, and suppress neuroinflammation. Conversely, dysbiosis may increase intestinal permeability, lipopolysaccharide translocation, systemic inflammation, and microglial activation. However, evidence remains heterogeneous and largely observational or experimental. Conclusions: The MD may promote neuroprotection through interconnected diet-microbiome-immune pathways. Longitudinal and intervention studies integrating microbiome, metabolomic, inflammatory, neuroimaging, and cognitive measures are needed to establish causality and advance precision nutrition strategies to prevent neurodegenerative disease.