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Probiotics, with their strong colonization capabilities, present a novel approach to drug delivery. Various engineering strategies have been developed to enhance the targeting ability of probiotics to inflammation sites, enabling precise delivery or in situ synthesis of therapeutic molecules to expand their multifunctional potential. This review discusses the recent advancements in bacterial modifications, including surface physico-chemical and biological coating, genetic engineering, outer membrane vesicles, minicells, and bacterial ghosts, all of which can enhance therapeutic localization. We also outline critical preclinical considerations, such as delivery frequency, systemic distribution, immune evasion, and gene contamination risks, for clinical translation. These engineered bacteria and bacterial derivatives hold great promise for personalized and sustained IBD treatments, providing a new frontier for therapy tailored to the complex inflammatory environment of IBD.<\/jats:p>","DOI":"10.1042\/ebc20253003","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T12:07:41Z","timestamp":1740658061000},"page":"169-179","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Engineered bacteria and bacterial derivatives as advanced therapeutics for inflammatory bowel disease"],"prefix":"10.1042","volume":"69","author":[{"given":"Jingyuan","family":"Wu","sequence":"first","affiliation":[{"name":"1School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlin","family":"Ye","sequence":"additional","affiliation":[{"name":"1School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"1School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China"},{"name":"2NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuoyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"1School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. 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