{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T11:19:22Z","timestamp":1793963962987,"version":"4.8.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008340","name":"UCLA Health System","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008340","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Increased intestinal permeability is a possible pathophysiological mechanism of irritable bowel syndrome (IBS). Increased colonic epithelial permeability is associated with visceral nociception in rodents and abdominal pain severity in IBS patients. Although IBS is more common in women, most studies on IBS-associated epithelial dysfunction have largely overlooked sex as a biologic variable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Men and women with Rome III- and Rome IV-positive IBS and HCs rated GI symptoms including abdominal pain severity at baseline, 24\u00a0h prior and immediately post procedure. Epithelial function was assessed <jats:italic>ex vivo<\/jats:italic> in Ussing chambers using sigmoid colon biopsies, by monitoring short-circuit current (Isc), transepithelial electrical resistance (TEER) and mucosal permeability to FITC-dextran 4\u00a0kDa (FD4). Biopsies tight junction protein mRNA expression was assessed using RNA seq. Statistical analyses included a framework of General Linear Models and linear contrast analyses performed using R software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>44 IBS patients (66% women, 30\u00a0years) and 19\u00a0HCs (53% women, 28\u00a0years) were enrolled. The proportion of women was not different between groups. As a group, IBS patients exhibited lower TEER compared to HCs (16.9 \u00b1 5.5 vs. 21.5 \u00b1 6.5\u00a0\u03a9\/cm<jats:sup>2<\/jats:sup>, p = 0.01, FDR = 0.02), but no difference in FD4 serosal concentration or Isc (basal or stimulated). Within men, IBS had lower TEER vs. HCs, but there was no disease difference within women. Independent of diagnosis, women had 1.3-fold lower TEER concentration and 1.5-fold higher FD4 serosal concentration than men. These sex differences were also seen within HCs, although within IBS, FD4 permeability only showed a trend to be higher in women vs. men. Abdominal pain ratings and IBS severity scores were not associated with TEER or FD4 concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our study confirms prior reports that IBS patients demonstrate altered sigmoid colonic epithelial function and shows for the first time that these are independent of sex. However, sex differences in sigmoid colonic epithelial function are observed independently of disease status. Further studies are needed to delineate if intestinal permeability interacts with other factors in the pathophysiology of IBS and if these interactions differ by sex.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2025.1509935","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:35:26Z","timestamp":1740119726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex-dependent alterations of colonic epithelial permeability: relevance to irritable bowel syndrome"],"prefix":"10.3389","volume":"16","author":[{"given":"Muriel","family":"Larauche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapna","family":"Mahurkar-Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Biraud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeran A.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.pain.2004.10.002","article-title":"Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase","volume":"113","author":"Ait-Belgnaoui","year":"2005","journal-title":"Pain"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020135","article-title":"Intestinal mucosal mast cells: key modulators of barrier function and homeostasis","volume":"8","author":"Albert-Bayo","year":"2019","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"105994","DOI":"10.1016\/j.psyneuen.2022.105994","article-title":"Not within spitting distance: salivary immunoassays of estradiol have subpar validity for predicting cycle phase","volume":"149","author":"Arslan","year":"2023","journal-title":"Psychoneuroendocrinology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020236","article-title":"Impaired intestinal permeability of tricellular tight junctions in patients with irritable bowel syndrome with mixed bowel habits (IBS-M)","volume":"12","author":"Awad","year":"2023","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.07.004","article-title":"Molecular mechanisms underlying loss of vascular and epithelial integrity in irritable bowel syndrome","author":"Barbaro","year":"2024","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1053\/j.gastro.2017.06.051","article-title":"Vasoactive intestinal polypeptide and mast cells regulate increased passage of colonic bacteria in patients with irritable bowel syndrome","volume":"153","author":"Bednarska","year":"2017","journal-title":"Gastroenterology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1038\/ajg.2011.257","article-title":"The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype","volume":"106","author":"Bertiaux-Vanda\u00eble","year":"2011","journal-title":"Am. 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