{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:16:16Z","timestamp":1791324976746,"version":"4.3.1"},"reference-count":89,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1F32DK117607\u201001A1"],"award-info":[{"award-number":["1F32DK117607\u201001A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The incidence of type 1 diabetes (T1D) is increasing annually, in addition to other childhood\u2010onset autoimmune diseases. This review is inspired by recent strides in research defining the pathophysiology of autoimmunity in celiac disease, a disease that has significant genetic overlap with T1D. Population genetic studies have demonstrated an increased proportion of newly diagnosed young children with T1D also have a higher genetic risk of celiac disease, suggesting that shared environmental risk factors are driving the incidence of both diseases. The small intestine barrier forms a tightly regulated interface of the immune system with the outside world and largely controls the mucosal immune response to non\u2010self\u2010antigens, dictating the balance between tolerance and immune response. Zonulin is the only known physiological modulator of the intercellular tight junctions, important in antigen trafficking, and therefore, is a key player in regulation of the mucosal immune response. While usually tightly controlled, when the zonulin pathway is dysregulated by changes in microbiome composition and function, antigen trafficking control is lost, leading to loss of mucosal tolerance in genetically susceptible individuals. The tenant of this hypothesis is that loss of tolerance would not occur if the zonulin\u2010dependent intestinal barrier function is restored, thereby preventing the influence of environmental triggers in individuals genetically susceptible to autoimmunity. This review outlines the current research and a structured hypothesis on how a dysregulated small intestinal epithelial barrier, a \u201cleaky gut,\u201d may be important in the pathogenesis of autoimmunity in certain individuals at risk of both T1D and celiac disease.<\/jats:p>","DOI":"10.1002\/dmrr.3309","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T10:40:01Z","timestamp":1584009601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-3085","authenticated-orcid":false,"given":"Lauren K.","family":"Wood Heickman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology University of Virginia  Charlottesville Virginia 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