{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:00Z","timestamp":1785422700103,"version":"3.56.0"},"reference-count":173,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100024026","name":"Marshall University Joan C. Edwards School of Medicine","doi-asserted-by":"crossref","award":["146"],"award-info":[{"award-number":["146"]}],"id":[{"id":"10.13039\/100024026","id-type":"DOI","asserted-by":"crossref"}]},{"award":["146"],"award-info":[{"award-number":["146"]}],"id":[{"id":"https:\/\/ror.org\/02erqft81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) is increasingly recognized as a systemic inflammatory disorder associated with elevated long-term risk of ischemic stroke, even among younger individuals without traditional vascular risk factors. Although chronic inflammation, endothelial dysfunction, and hypercoagulability partially explain this association, the biological mechanisms linking intestinal inflammation to cerebral vascular injury remain incompletely defined. Extracellular vesicles (EVs), membrane-bound particles released by epithelial, immune cells and platelets, have emerged as potent mediators of intercellular communication in inflammatory states. In IBD, circulating EVs are enriched with pro-inflammatory cytokines, microRNAs, adhesion molecules, tissue factors, which are capable of promoting endothelial activation, blood\u2013brain barrier disruption, immune-thrombosis and neuroinflammation. This review summarizes epidemiologic, vascular, and EV biology literature to propose a mechanistic framework in which EV-mediated signaling integrates intestinal inflammation with cerebrovascular vulnerability along the gut\u2013vascular\u2013brain axis. While direct causal evidence remains limited, converging mechanistic data supports biological plausibility and defines priorities for future experimental and translational investigation.<\/jats:p>","DOI":"10.3390\/biom16040577","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T08:14:17Z","timestamp":1776154457000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles in the Gut\u2013Vascular\u2013Brain Axis: A Missing Mechanistic Link Between IBD and Stroke Risk"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7908-4050","authenticated-orcid":false,"given":"Harshal","family":"Sawant","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. 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Edwards School of Medicine, Marshall University, Huntington, WV 25755-0001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-284X","authenticated-orcid":false,"given":"Subha","family":"Arthur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755-0001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Luo, C., Liu, L., Zhu, D., Ge, Z., Chen, Y., and Chen, F. (2025). Risk of stroke in patients with inflammatory bowel disease: A systematic review and meta-analysis. 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