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IBD results from a triad of immune, environmental (eg, gut microbiome), and genetic (including epigenetic) mechanisms, and therefore has been subject to a wide variety of therapeutic strategies. Among these, the administration of probiotics, particularly Gram-positive lactic acid bacteria (LAB), targeting both immune and environmental factors, has shown promising potential for efficacy in selected populations in early clinical trials. However, knowledge gaps and inconsistent efficacy currently prevent recommendations for the use of probiotics in larger IBD patient populations. The inconsistent efficacy of probiotics is likely due to variable cell viability and potency after administration, further exacerbated by IBD patient heterogeneity. Thus, an alternative to live probiotics for IBD has emerged in the form of bacterial extracellular vesicles (BEVs)\u2014cell-secreted nanovesicles containing abundant bioactive cargo that, like live probiotics, can regulate immune and environmental factors but with fewer viability limitations and safety concerns. In this review, we summarize the work done to date establishing the potential of BEVs to provide the therapeutic benefits in IBD and discuss the hurdles BEVs must overcome to achieve clinical translation. We also consider future directions for BEV therapeutics, especially treatment potential for necrotizing enterocolitis (NEC), which shares similarities in pathophysiology with IBD.<\/jats:p>","DOI":"10.1093\/ibd\/izaf107","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T07:55:53Z","timestamp":1745394953000},"page":"1723-1739","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Potential and Translational Challenges for Bacterial Extracellular Vesicles in Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"31","author":[{"given":"Nicholas H","family":"Pirolli","sequence":"first","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland , College Park, MD 20742 ,","place":["USA"]},{"name":"Robert E. Fischell Institute for Biomedical Devices, University of Maryland , College Park, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Raufman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine , Baltimore, MD ,","place":["USA"]},{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine , Baltimore, MD ,","place":["USA"]},{"name":"Biomedical Laboratory Research and Development Service, Veterans Affairs Maryland Healthcare System , Baltimore, MD ,","place":["USA"]},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center , Baltimore, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-5988","authenticated-orcid":false,"given":"Steven M","family":"Jay","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland , College Park, MD 20742 ,","place":["USA"]},{"name":"Robert E. Fischell Institute for Biomedical Devices, University of Maryland , College Park, MD ,","place":["USA"]},{"name":"Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center , Baltimore, MD ,","place":["USA"]},{"name":"Program in Molecular and Cell Biology, University of Maryland , College Park, MD 20742 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"issue":"1","key":"2025061403565715000_CIT0001","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/s2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"5","author":"GBD 2019 IMID Collaborators","year":"2020","journal-title":"Lancet Gastroenterol 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