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Melanin, a natural biopolymer with robust anti\u2010inflammatory and antioxidant properties, presents a promising treatment avenue for UC. Probiotics, particularly\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917 (EcN), have gained recognition for their role in restoring gut homeostasis. In this study, we genetically engineered EcN to overexpress tyrosinase (EcN\u2010T), facilitating the biosynthesis of melanin specifically for UC treatment. The engineered probiotics demonstrated superior therapeutic efficacy compared to either melanin or EcN administered alone, highlighting a synergistic effect. EcN\u2010T not only exhibited significant capabilities in scavenging reactive oxygen species and restoring gut microbiota but also possessed the characteristic of enhancing gut colonization time, thereby extending the dosing frequency. Moreover, EcN\u2010T showcased novel mechanisms, such as the restoration of the intestinal mucosal barrier and the elevation of short\u2010chain fatty acid levels. Additionally, EcN\u2010T inhibited M1 macrophage polarization through Hypoxia\u2010Inducible Factor 1\u2010alpha (HIF\u20101\u03b1)dependent glycolytic reprogramming, underscoring its immunomodulatory potential. Collectively, these findings provide new insights into the therapeutic potential of EcN\u2010T for UC treatment, offering a novel strategy that enhances treatment efficacy while potentially reducing side effects associated with conventional therapies.\n                  <\/jats:p>","DOI":"10.1002\/btm2.70067","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:04:45Z","timestamp":1756461885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineered probiotic alleviates ulcerative colitis by inhibiting\n                    <scp>M1<\/scp>\n                    macrophage polarization via glycolytic reprogramming"],"prefix":"10.1002","volume":"10","author":[{"given":"Chaoqun","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine Daping Hospital, Army Medical University  Chongqing 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