{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:48:13Z","timestamp":1789850893878,"version":"4.0.1"},"reference-count":74,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,10]],"date-time":"2019-02-10T00:00:00Z","timestamp":1549756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373756"],"award-info":[{"award-number":["81373756"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intestinal barrier dysfunction is a key etiologic factor of irritable bowel syndrome (IBS). Metformin improves intestinal barrier function, although the underlying mechanism has yet to be fully explained. This study evaluates the protective effect of metformin on colonic barrier integrity and explores the underlying cellular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IBS\u2010like rats were induced by maternal separation. Metformin was administered daily by gavage at 08:30, and rat pups were then separated from their mother. Visceral hyperalgesia and depression\u2010like behaviors were evaluated by colorectal distension, sucrose preference tests, and forced swimming tests. Intestinal integrity was analyzed using sugar probes and transmission electron microscopy. Inflammatory factors and the levels of corticotropin\u2010releasing factor were assessed by PCR and ELISA. The number of mast cells was evaluated by toluidine blue staining. Protein expression and localization were determined using Western blot and immunochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Metformin pretreatment (a) reduced visceral hypersensitivity to colorectal distension, immobility time and enhanced sucrose consumption; (b) decreased urine lactulose\/mannitol ratio and sucralose output; (c) inhibited the dilation of tight junction and prevented claudin\u20104 translocation; (d) inhibited mast cell activation and downregulated the expression of IL\u20106, IL\u201018, tryptase, PAR\u20102, and ERK activation; (e) inhibited claudin\u20104 phosphorylation at serine sites and interactions between clau\u20104 and ZO\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Metformin may block mast cell activation to reduce PAR\u20102 expression and subsequently inhibit ERK activation and clau\u20104 phosphorylation at serine sites to normalize the interaction of clau\u20104 and ZO\u20101 and clau\u20104 distribution. Metformin may be clinically beneficial for patients with IBS or IBS\u2010like symptoms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13556","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T06:25:31Z","timestamp":1549866331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation\u2010induced IBS\u2010like rats"],"prefix":"10.1111","volume":"31","author":[{"given":"Yong","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Neuronal Network and Systems Biology, School of Basic Medical Sciences Shanghai Medical College, Fudan University Shanghai China"},{"name":"Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders Hubei University of Science and Technology Xianning 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