{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:23:39Z","timestamp":1793816619807,"version":"4.6.1"},"reference-count":145,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21AI144738-24"],"award-info":[{"award-number":["1R21AI144738-24"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Globally, Parkinson\u2019s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut\u2013brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called \u201cleaky gut,\u201d allows harmful substances, toxins, and misfolded \u03b1-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading \u03b1-synuclein pathology to the brain through the vagus nerve or compromised blood\u2013brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms26199593","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:06:02Z","timestamp":1759316762000},"page":"9593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Gut Permeability and Microbiota in Parkinson\u2019s Disease: Mechanistic Insights and Experimental Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"given":"Yicheng","family":"Liang","sequence":"first","affiliation":[{"name":"College of Biological Science, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA"},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-0261","authenticated-orcid":false,"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Wen","family":"Su","sequence":"additional","affiliation":[{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41531-018-0058-0","article-title":"Prevalence of Parkinson\u2019s disease across North America","volume":"4","author":"Marras","year":"2018","journal-title":"NPJ Park. 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