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However, challenges such as low bacterial survival under harsh gastrointestinal conditions, difficulties in achieving long\u2010term colonization, and unclear therapeutic targets limit their effectiveness. To address these issues, a novel approach is proposed that integrates genetic and chemical engineering for intestinal flora regulation in UC treatment. This strategy employs bacterial programmability and gene editing to produce bactericidal agents that dynamically modulate the intestinal microecology and utilize controlled chemical modifications to enhance bacterial resistance. Using\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    Nissle 1917 (EcN) as a model, a polyelectrolyte composite coating is developed that significantly increased bacterial survival in the gastrointestinal tract\u201440\u2010fold in the stomach and 74\u2010fold in the small intestine. Additionally, EcN::mcmA is engineered to overproduce iron\u2010carrier microcins (MccM) with a \u201cTrojan horse\u201d mechanism to target and disrupt pathogenic bacteria. In a dextran sulfate sodium (DSS)\u2010induced mouse UC model, EcN::mcmA@P\/O treatment effectively reduced inflammation and improved intestinal flora regulation, presenting a promising and potentially safer long\u2010term solution for UC.\n                  <\/jats:p>","DOI":"10.1002\/adma.202417050","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T22:13:18Z","timestamp":1748815998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Synergistic Genetic and Chemical Engineering of Probiotics for Enhanced Intestinal Microbiota Regulation and Ulcerative Colitis Treatment"],"prefix":"10.1002","volume":"37","author":[{"given":"Jiani","family":"Jiang","sequence":"first","affiliation":[{"name":"National Engineering Research Center of Rice and Byproduct Deep Processing College of Food Science and Engineering Central South University of Forestry and Technology  Changsha 410004 P. R. 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