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Our study aimed to characterize the mechanism by which the toxin leads to diarrhea via epithelial barrier dysfunction in a small intestine Caco\u20102 cell model. Microcystin\u2010treated human Caco\u20102 epithelial monolayers were functionally and molecularly analyzed for barrier dysfunction. Tight junctions (TJs) and cell damage were analyzed in relation to transepithelial electrical resistance (TER) changes. TER of microcystin\u2010treated Caco\u20102 cells was reduced by 65% of the initial value after 24 h; concomitantly, permeability for fluorescein increased 2.6\u2010fold. Western blot analysis showed reduced claudin\u20101 expression, while expression of claudin\u20103 and \u20104 remained unchanged. Super\u2010resolution stimulated emission depletion microscopy revealed that TJ integrity was compromised by fraying and splitting of the TJ domain of the epithelial cells. Epithelial apoptosis did not significantly contribute to epithelial barrier dysfunction, while cytoskeletal actomyosin constriction was associated with TJ disintegration and the barrier defect. Our results indicate that microcystin causes intestinal barrier leakiness, which helps to explain the leak flux type of diarrhea as the main pathomechanism after ingestion of cyanobacterial toxin.<\/jats:p>","DOI":"10.1111\/nyas.14870","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T04:15:16Z","timestamp":1658895316000},"page":"188-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Unraveling the intestinal epithelial barrier in cyanotoxin microcystin\u2010treated Caco\u20102 cell monolayers"],"prefix":"10.1111","volume":"1516","author":[{"given":"Jan\u2010Leo","family":"Kaak","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Infectious Diseases and Rheumatology, Clinical Physiology\/Nutritional Medicine Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bia 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