{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:13:56Z","timestamp":1790187236016,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["GRK 2318\u2014318905415"],"award-info":[{"award-number":["GRK 2318\u2014318905415"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["DFG Schu 559\/11-5\u2014175142815"],"award-info":[{"award-number":["DFG Schu 559\/11-5\u2014175142815"]}]},{"name":"German Research Foundation and the Open Access Publication Fund of the Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin","award":["GRK 2318\u2014318905415"],"award-info":[{"award-number":["GRK 2318\u2014318905415"]}]},{"name":"German Research Foundation and the Open Access Publication Fund of the Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin","award":["DFG Schu 559\/11-5\u2014175142815"],"award-info":[{"award-number":["DFG Schu 559\/11-5\u2014175142815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: In patients with diarrhea-predominant irritable bowel syndrome (IBS-D), the diarrheal mechanisms are largely unknown, and they were examined in this study on colon biopsies. Methods: Electrophysiological measurements were used for monitoring functional changes in the diarrheic colon specimens. In parallel, tight junction protein expression was analyzed by Western blot and confocal laser-scanning microscopy, and signaling pathway analysis was performed using RNA sequencing and bioinformatics. Results: Epithelial resistance was decreased, indicating an epithelial leak flux diarrheal mechanism with a molecular correlate of decreased claudin-1 expression, while induction of active anion secretion and impairment of active sodium absorption via the epithelial sodium channel, ENaC, were not detected. The pathway analysis revealed activation of barrier-affecting cytokines TNF-\u03b1, IFN-\u03b3, IL-1\u03b2 and IL-4. Conclusions: Barrier dysfunction as a result of epithelial tight junction changes plays a role in IBS-D as a pathomechanism inducing a leak flux type of diarrhea.<\/jats:p>","DOI":"10.3390\/cells12242846","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T06:53:16Z","timestamp":1702623196000},"page":"2846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Epithelial Barrier Dysfunction in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) via Downregulation of Claudin-1"],"prefix":"10.3390","volume":"12","author":[{"given":"Karem","family":"Awad","sequence":"first","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Barmeyer","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bojarski","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-726X","authenticated-orcid":false,"given":"Oliver","family":"Nagel","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Fah M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4672-0623","authenticated-orcid":false,"given":"Michal R.","family":"Schweiger","sequence":"additional","affiliation":[{"name":"Institute for Translational Epigenetics, Medical Faculty, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-5521","authenticated-orcid":false,"given":"J\u00f6rg-Dieter","family":"Schulzke","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-4146","authenticated-orcid":false,"given":"Roland","family":"B\u00fccker","sequence":"additional","affiliation":[{"name":"Clinical Physiology\/Nutritional Medicine, Department of Gastroenterology, Infectious Diseases and Rheumatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1463897","DOI":"10.1080\/21688370.2018.1463897","article-title":"Pathophysiology of IBD associated diarrhea","volume":"6","author":"Anbazhagan","year":"2018","journal-title":"Tissue Barriers"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Karnsakul, W., and Lifschitz, C. 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