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Current animal models are limited in the generation of germ\u2010free animals to evaluate the roles of gut bacteria in intestinal health. Here, we used the honeybee (\n                    <jats:italic>Apis mellifera<\/jats:italic>\n                    ) as a model animal to develop colitis\u2010like gut permeability induced by dextran sodium sulfate (DSS) treatment. We found that DSS could increase gut permeability and compromise the mucosal barrier in honeybees, resulting in decreased survival rates, midgut elongation, and intestinal edema. DSS treatment upregulated the expression of\n                    <jats:italic>wnt\u20101<\/jats:italic>\n                    and\n                    <jats:italic>rhomboid<\/jats:italic>\n                    and downregulated the pathways of cytochrome P450 (CYP) and the peroxisome proliferator\u2010activated receptor signaling. Moreover, DSS disrupted the structure and functional profiles of the gut microbiota. Our results showed that medications reduced mortality and moderated leaky gut syndrome in DSS\u2010treated bees. Notably, 5\u2010aminosalicylic acid (5\u2010ASA) could attenuate gut permeability in honeybees through activating PPAR\n                    <jats:italic>\u03b3<\/jats:italic>\n                    signaling, which mimics the human. Honeybees offer a promising experimental model for investigating the etiology of intestinal diseases and disentangling the roles of gut symbionts in intestinal health.\n                  <\/jats:p>","DOI":"10.1111\/1744-7917.13508","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:04:51Z","timestamp":1739858691000},"page":"231-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dextran sodium sulfate\u2010induced colitis\u2010like gut permeability and dysbiosis in honeybees"],"prefix":"10.1111","volume":"33","author":[{"given":"Ya","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieteng","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering 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