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Using multi\u2010omics and fecal microbiota transplantation (FMT) in human microbiota\u2010associated (HMA) mice, this study explored rapamycin\u2010induced gut dysbiosis and its impacts on islet function and inflammation post\u2010ICT. ICT significantly altered the gut microbiota of type 2 diabetes mellitus (T2DM) patients, and FMT from these patients to antibiotic\u2010treated mice recapitulated metabolic disorders in the mice. These disorders included hyperglycemia, hepatic and pancreatic injury, and impaired intestinal barrier. Rapamycin decreased beneficial bacteria (\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    ,\n                    <jats:italic>Faecalibacterium<\/jats:italic>\n                    ) and enriched\n                    <jats:italic>Desulfovibrio<\/jats:italic>\n                    in HMA\u2010T2DM mice. Targeted microbial modulation by chitooligosaccharides (COS) ameliorated rapamycin\u2010induced deficits in insulin and C\u2010peptide secretion, as well as elevated glycated hemoglobin levels. COS also significantly reduced serum inflammatory markers IP\u201010 and MCP\u20101, while upregulating colonic barrier proteins (\n                    <jats:italic>Muc2<\/jats:italic>\n                    ,\n                    <jats:italic>Occludin<\/jats:italic>\n                    ) in HMA\u2010T2DM\u2010ICT mice. COS additionally mitigated postoperative hyperglycemia via the PI3K\/AKT\/GSK3\u03b2\/FOXO1 signaling pathway. This study identified COS as a microbiota\u2010targeted adjunctive strategy to improve metabolic recovery and islet function under post\u2010transplant immunosuppression.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72122","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:37:38Z","timestamp":1784288258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota\u2010Targeted Chitooligosaccharides Intervention Restores Glucose Homeostasis After Islet Cell Transplantation in Rapamycin\u2010Treated Mice"],"prefix":"10.1002","volume":"14","author":[{"given":"Kunlin","family":"Chang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering, School of Biotechnology East China University of Science and Technology  Shanghai 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