Role of Hesperidin in Ulcerative Colitis: From Barrier Protection and Immune Regulation to Microbiota–Host Interaction

High Resolution Image Download MS PowerPoint Slide Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by a self-perpetuating cycle of intestinal barrier dysfunction, immune dysregulation, and microbial dysbiosis. Current therapies often face limitations in safety, long-term efficacy, and costs. Hesperidin, a natural citrus flavonoid, has emerged as a promising therapeutic candidate due to its high safety margin and pleiotropic efficacy. This review systematically elaborates hesperidin’s mechanisms in UC, involving the enhancement of the intestinal barrier, modulation of immune responses, and reprogramming of microbial homeostasis. We further discuss the importance of microbial metabolites, particularly short-chain fatty acids, bile acids, and tryptophan metabolites, in the pathogenesis of UC. Notably, we propose a novel hypothesis that hesperidin facilitates the restoration of intestinal barrier and immune homeostasis by modulating the gut microbiota–tryptophan–aryl hydrocarbon receptor (AhR) signaling axis. Collectively, this work provides a theoretical foundation for developing hesperidin as a therapeutic candidate for UC and a key component in functional foods.