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This study developed a chitosan-based controlled-release microsphere (CBMS) treatment to overcome these issues. CBMS utilizes the mucoadhesive properties of chitosan to achieve targeted, controlled UCB release in the colon, enhancing its stability and bioavailability. In a DSS-induced UC mouse model, CBMS alleviated clinical symptoms, reduced colon shortening, and improved histological outcomes, including reduced inflammation and enhanced mucosal repair. The mechanism involves CBMS retention in the intestinal lumen, UCB inactivation of digestive proteases, and restoration of microbiota balance, suppressing pro-inflammatory pathways. CBMS offers a promising new therapeutic strategy for UC and insights into polysaccharide-based drug delivery systems.<\/jats:p>","DOI":"10.3390\/biom16081140","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"1140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chitosan\u2013Unconjugated Bilirubin Microspheres Alleviate Dysbiosis, Immune Dysregulation, and Intestinal Barrier Damage in Ulcerative Colitis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-806X","authenticated-orcid":false,"given":"Xinyu","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences, WU Lien-Teh Institute, Harbin Medical University, Harbin 150081, China"},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences, WU Lien-Teh Institute, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-1927","authenticated-orcid":false,"given":"Fengmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences, WU Lien-Teh Institute, Harbin Medical University, Harbin 150081, China"},{"name":"Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7673-0293","authenticated-orcid":false,"given":"Xiuhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"},{"name":"Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1161\/ATVBAHA.114.303279","article-title":"Risk of ischemic stroke and decreased serum bilirubin levels: Is there a causal link?","volume":"34","author":"Targher","year":"2014","journal-title":"Arterioscler. 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