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Here, we demonstrate that oral vancomycin alleviates colitis symptoms in murine models, mirroring its clinical efficacy in inducing remission in patients with UC. Mechanistically, vancomycin\u2019s therapeutic effect is achieved by reducing deoxycholic acid (DCA). We reveal that DCA impairs mucosal repair driven by group 2 innate lymphoid cells (ILC2s) by inducing ER stress through direct binding to thioredoxin-related transmembrane protein 2 (TMX2). This interaction disrupts TMX2\u2019s role in protein folding, triggering unresolved unfolded protein response via hyperactivation of PERK\/eIF2\u03b1 signaling, which suppresses the production of pro-healing molecules by ILC2s. Pharmacological inhibition of PERK phosphorylation restores ILC2 function and accelerates colitis resolution. Our work uncovers a pathogenic microbiota\/DCA\/ILC2 axis that obstructs mucosal healing and positions vancomycin as a targeted strategy to eliminate DCA, thereby promoting UC remission.<\/jats:p>","DOI":"10.1172\/jci.insight.197470","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:00:46Z","timestamp":1775584846000},"source":"Crossref","is-referenced-by-count":3,"title":["Vancomycin eliminates gut deoxycholic acid, restoring ER proteostasis in ILC2s and relieving colitis"],"prefix":"10.1172","volume":"11","author":[{"given":"Qiuheng","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Qilu Hospital of Shandong University, Advanced Medical Research Institute, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Qilu Hospital of Shandong University, Advanced Medical 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