{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:06:24Z","timestamp":1790251584830,"version":"4.1.0"},"reference-count":143,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) and Parkinson\u2019s 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\u2013brain 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\u2013microbiome\u2013immune 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.<\/jats:p>","DOI":"10.3390\/nu18193146","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:11:23Z","timestamp":1790248283000},"page":"3146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiome-Mediated Neuroprotective Effect of the Mediterranean Diet: A Narrative Review of Cognitive Aging, Alzheimer\u2019s Disease, and Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Kundun","family":"Kamalakar","sequence":"first","affiliation":[{"name":"Departments of Psychiatry and Pharmacology, Institute of Translational Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5010-5961","authenticated-orcid":false,"given":"Christa","family":"Akerele","sequence":"additional","affiliation":[{"name":"Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Lafont","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Pharmacology, Institute of Translational Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8155-8017","authenticated-orcid":false,"given":"Lauren R.","family":"Koralnik","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Gilman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Albert Einstein College of Medicine, New York City, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Clemente","family":"Litran","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Genomic Sciences and Immunology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakleen","family":"Lee","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-8873","authenticated-orcid":false,"given":"Jessica","family":"Robinson-Papp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Malaspina","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Pharmacology, Institute of Translational Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"04160","DOI":"10.7189\/jogh.13.04160","article-title":"Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide","volume":"13","author":"Huang","year":"2023","journal-title":"J. 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