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To address these challenges, an inodorous macromolecule \u03b2\u2010glucan\u2010BA (GLU\u2010BA) is synthesized via one\u2010step esterification, allowing for BA production in the intestine with burst yet gradual dynamics. After oral administration, GLU\u2010BA self\u2010assembles into nanomicelles, preventing premature gastric absorption. Upon reaching the intestine, endogenous esterases rapidly hydrolyze its ester bonds, triggering a burst BA release while exposing GLU, with the GLU subsequently metabolized by gut microbiota to gradually generate BA. Such sequential production enabled by a single oral administration of GLU\u2010BA ensures significant intestinal BA availability as early as 0.5\u00a0h post administration, lasting for at least 12\u00a0h. This leads to co\u2010achievement of prompt intervention and sustained therapeutic efficacy, as demonstrated in mouse models of ulcerative colitis and immunosuppression. Additionally, GLU\u2010BA restores gut microbiota dysbiosis, during which BA\u2010producing bacteria are enriched, reinforcing BA intestinal replenishment. With excellent biocompatibility (negligible toxicity after 366 days of daily oral administration), scalable synthesis (\u223c54\u00a0g per one\u2010pot reaction), and broad\u2010spectrum bioactivities of BA, GLU\u2010BA demonstrates to be a promising candidate for clinical applications in treating diseases associated with intestinal disorders.<\/jats:p>","DOI":"10.1002\/advs.77454","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:59:26Z","timestamp":1787846366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Nanomicelle\u2010Mediated Sequential Butyrate Production in the Intestine for Ulcerative Colitis and Immunosuppression Treatment"],"prefix":"10.1002","author":[{"given":"Feifei","family":"Xin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Nanchang University  Nanchang Jiangxi People's Republic of 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