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Oral probiotics are a potential treatment for IBD. However, the limited colonization and lack of sustained activity in the inflamed colon are challenging. In this research, mucosal colonized engineered\n                    <jats:italic>Nissle 1917<\/jats:italic>\n                    (\n                    <jats:italic>EcN<\/jats:italic>\n                    ) was designed for targeted gut delivery and restored microbiota homeostasis in IBD. 2\u2010iminothiolane thiolation was modified on the surface of\n                    <jats:italic>EcN<\/jats:italic>\n                    , thus the employed disulfide bonds can targeted bind with intestinal mucus layer, enhancing\n                    <jats:italic>EcN<\/jats:italic>\n                    activity and retention in the inflamed colon so that the gut microbiota homeostasis can be restored effectively. Further, we developed a probiotic\u2010based therapeutic platform to load Ononin onto\n                    <jats:italic>EcN<\/jats:italic>\n                    via manganese mineralization (OME). Oral OME can colonize the intestine and deliver drugs to the inflamed colon, exhibiting synergistic targeted drug\u2010therapeutic effects and restoring macrobiotic homeostasis. Further mechanism study showed that OME ameliorates DSS\u2010induced intestinal inflammation by upregulating Eubacterium coprostanoligenes, which secretes methylmalonyl\u2010CoA mutase to modulate intestinal T cell proportions and functional polarization, ultimately restoring immune homeostasis. This research highlighted the potential of mucosal colonized engineered\n                    <jats:italic>EcN<\/jats:italic>\n                    to restore microbiota homeostasis and targeted delivery of drugs, offering a promising strategy for clinical applications.\n                  <\/jats:p>","DOI":"10.1002\/smll.202507578","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T07:45:55Z","timestamp":1766994355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucosal Colonized Engineered\n                    <i>Nissle 1917<\/i>\n                    for Targeted Gut Delivery and Restored Microbiota Homeostasis in Inflammatory Bowel Disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Hemin","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health Capital Medical University  Beijing P. R. 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