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This work aimed to define the timing of intestinal barrier dysfunction relative to central nervous system (CNS) changes in the A53T \u03b1-synuclein transgenic mouse model of PD. Functional and molecular assessments of the gastrointestinal tract (ileum and colon) were conducted at 12 and 36 weeks. We measured in vivo and ex vivo intestinal permeability, nutrient absorption, histomorphology, goblet cell density, and expression of MUC2 and Claudin-1. Inflammatory markers (CRP, TNF-\u03b1, CD45) were quantified in plasma and gut tissues. A53T mice exhibited increased intestinal permeability at 12 and 36 weeks, with transiently elevated ex vivo transepithelial electrical resistance (TER) at 12 weeks. Nutrient absorption remained intact. Morphological changes included widened villi and crypts, altered mucin expression, and early reductions in Claudin-1 in the ileum and the colon while inflammatory markers remained largely unchanged. These findings suggest that gut dysfunction precedes known central pathology in A53T mice, supporting further investigation into the gut as an early site of pathology and a potential therapeutic target in PD.<\/jats:p>","DOI":"10.1007\/s00441-026-04062-9","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:33:00Z","timestamp":1774315980000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early intestinal barrier changes in A53T transgenic Parkinson\u2019s disease mice"],"prefix":"10.1007","volume":"404","author":[{"given":"Myat Noe","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Artaiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Finkelstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanti","family":"Diwakarla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"McQuade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"4062_CR1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.ebiom.2019.05.064","volume":"44","author":"VTE Aho","year":"2019","unstructured":"Aho VTE, Pereira PAB, Voutilainen S, Paulin L, Pekkonen E, Auvinen P, Scheperjans F (2019) Gut microbiota in Parkinson\u2019s disease: temporal stability and relations to disease progression. 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