Preclinical Evidence for Prebiotic Therapy in Ulcerative Colitis: Mechanisms, Efficacy, and Translational Perspectives

Ulcerative colitis, a major form of inflammatory bowel disease, is strongly influenced by gut microbiota composition and metabolism. Prebiotics are nondigestible food ingredients that selectively stimulate beneficial intestinal bacteria and have emerged as promising strategies for mitigating colitis. 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-α], interleukin [IL]-1β, 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-immune-microbiota axes to relieve colitis, and establish a foundation for translating results from animal models into controlled human studies.