Objective:

The objective of this literature review is to examine how adherence to the Mediterranean diet may modulate the gut–brain axis (GBA) and provide a protective effect against the development of Alzheimer’s disease (AD). There are few reviews integrate diet, GBA, and AD pathogenesis simultaneously.

Background:

Alzheimer’s Disease (AD) is the most common neurodegenerative disease worldwide, with approximately 44 million people being affected from this form of dementia. Many factors contribute to the development of AD, with diet playing an important role, contributing many metabolites that may lead to pro- or anti-inflammatory responses. This is through the GBA, a pathway that connects the central nervous system to the gut microbiome, allowing for maximal interplay between the two systems within the body. The Mediterranean diet has been shown to play a protective role in the development of AD. 

Design/Methods:

This narrative review synthesizes recent human and animal studies identified through PubMed, EmBase, and Google Scholar searches (2009–2025) using keywords including Mediterranean diet, gut–brain axis, short-chain fatty acids, polyunsaturated fatty acids, and Alzheimer’s disease. Seminal studies prior to 2010 were also included to provide historical context.

Results:

Evidence indicates that the Mediterranean diet, characterized by high intake of plant-based foods, fish, olive oil, and polyphenols, is associated with beneficial modulation of the gut microbiome. Key mechanisms include increased production of short-chain fatty acids, maintenance of blood–brain barrier integrity, reduced neuroinflammation, and enhanced synaptic plasticity. Human cohort studies and randomized controlled trials suggest improved cognitive performance and slower cortical atrophy among individuals adhering to this diet, although findings are heterogeneous and adherence remains a limiting factor.

Conclusions:

The Mediterranean diet shows promise as a modifiable lifestyle intervention that supports brain health through GBA-mediated mechanisms. While preclinical and observational data are encouraging, more longitudinal, sex-stratified, and mechanistic human studies are needed to validate dietary prevention strategies for AD.