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This review summarizes recent evidence, with a primary focus on animal models, examining the effects of diverse prebiotic classes including pectic polysaccharides, exopolysaccharides, soluble and insoluble fibers, glucans, resistant starch, and novel enzymatically structured and chemically modified prebiotics. Across studies, these compounds consistently alleviated colitis through consistent multifactorial mechanisms: restoring gut microbiota diversity and richness, increasing the production of short-chain fatty acids (SCFAs), strengthening intestinal barrier integrity by upregulating tight junction proteins (zonula occludens 1 [ZO-1], occludin, claudin) and mucin production, and modulating immune responses by suppressing proinflammatory cytokines (tumor necrosis factor-alpha [TNF-\u03b1], interleukin [IL]-1\u03b2, IL-6) while promoting anti-inflammatory mediators (IL-10, T-regulatory [Treg] cells). Novel approaches, such as enzymatically synthesized oligosaccharides and structure-modified prebiotics, further demonstrated superior efficacy compared with natural counterparts, highlighting the potential of precision prebiotic therapy. Importantly, many promising candidates are derived from agricultural byproducts or microbial fermentation, offering cost-effective nutraceutical applications. Collectively, current findings provide mechanistic insights into how prebiotics act on gut\u2013immune\u2013microbiota axes to relieve colitis, and establish a foundation for translating results from animal models into controlled human studies.<\/jats:p>","DOI":"10.1093\/nutrit\/nuag011","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:51:00Z","timestamp":1768481460000},"source":"Crossref","is-referenced-by-count":3,"title":["Preclinical Evidence for Prebiotic Therapy in Ulcerative Colitis: Mechanisms, Efficacy, and Translational Perspectives"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0021-2473","authenticated-orcid":false,"given":"Mihad","family":"Omer","sequence":"first","affiliation":[{"name":"Department of Nephrology, University of Miami, Miller School of Medicine\/Jackson Health System , Miami, FL 33136,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassabelrasoul O","family":"Awad","sequence":"additional","affiliation":[{"name":"Health Care Facility; Imperial College London Diabetes and Endocrine Centre (ICLDEC) , Al Ain,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer I","family":"Omer","sequence":"additional","affiliation":[{"name":"Michigan Kidney Consultants P.C , 5280 Metro Parkway , Sterling Height, MI 48310,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim O","family":"Mohamed","sequence":"additional","affiliation":[{"name":"National Oilseeds Processing Research Institute, University of Gezira , Wad-Medani,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"2026022709342890000_nuag011-B1","doi-asserted-by":"publisher","first-page":"129346","DOI":"10.1016\/j.ijbiomac.2024.129346","article-title":"Alleviative effects of 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