{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T06:52:05Z","timestamp":1794034325869,"version":"4.8.0"},"reference-count":228,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"National Priorities Research Program","doi-asserted-by":"publisher","award":["NPRP 14S0311\u2013210033"],"award-info":[{"award-number":["NPRP 14S0311\u2013210033"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Neurodegenerative disorders such as Alzheimer\u2019s disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within the gut\u2013brain axis largely depends on the gut microbiota and its metabolites. This review explores the intricate molecular mechanisms linking gut microbiota dysbiosis to cognitive decline, emphasizing the impact of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, on neuroinflammation, blood\u2013brain barrier (BBB) integrity, and amyloid-\u03b2 and tau pathology. The paper highlights major microbiome signatures associated with Alzheimer\u2019s disease, detailing their metabolic pathways and inflammatory crosstalk. Dietary interventions have shown promise in modulating gut microbiota composition, potentially mitigating neurodegenerative processes. This review critically examines the influence of dietary patterns, such as the Mediterranean and Western diets, on microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 fatty acids, and polyphenols exhibit neuroprotective effects by modulating gut microbiota and reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), as potential interventions for slowing Alzheimer\u2019s progression. Despite these advances, several knowledge gaps remain, including interindividual variability in microbiome responses to dietary interventions and the need for large-scale, longitudinal studies. The study proposes an integrative, precision medicine approach, incorporating microbiome science into Alzheimer\u2019s treatment paradigms. Ultimately, cognizance of the gut\u2013brain axis at a mechanistic level could unlock novel therapeutic avenues, offering a non-invasive, diet-based strategy for managing neurodegeneration and improving cognitive health.<\/jats:p>","DOI":"10.3390\/foods14091559","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"1559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Could a Mediterranean Diet Modulate Alzheimer\u2019s Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4155-5819","authenticated-orcid":false,"given":"Alice N.","family":"Mafe","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Sciences, Taraba State University, Main Campus, Jalingo 660101, Taraba State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-3366","authenticated-orcid":false,"given":"Dietrich","family":"B\u00fcsselberg","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha Metropolitan Area, Ar-Rayyan P.O. Box 22104, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, S., Jiang, Y., Yang, A., Meng, F., and Zhang, J. (2024). The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need. Aging Dis., Online ahead of print.","DOI":"10.14336\/AD.2024.1071"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2024). 2024 Alzheimer\u2019s Disease Facts and Figures. Alzheimer\u2019s Dement., 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3233\/JAD-240163","article-title":"Societal Costs of Dementia: 204 Countries, 2000\u20132019","volume":"101","author":"Lastuka","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"(2020). 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