Metabolic reprogramming in ulcerative colitis: integrating dietary drivers, pathogenesis, and therapeutic advances

Ulcerative colitis (UC) is a complex disorder characterized by gene-environment interactions that compromise the integrity of the mucosa and submucosa. The current evidence indicates a significant correlation between the increasing incidence of UC and the consumption of a Western diet. Dietary patterns alter the nutritional composition, thus inducing metabolic shifts in the intestinal microenvironment that disrupt gut homeostasis and contribute to the development of UC. Mechanistically, metabolic abnormalities in epithelial cells, macrophages, neutrophils, and other cell types compromise the integrity of the intestinal epithelial barrier and modulate immune-inflammatory responses, promoting the onset and progression of UC. Furthermore, the dysregulation of microbial metabolites disrupts gut microbiota homeostasis, contributing to disease progression. Here, we summarize the association between the dietary pattern and UC risk; we further elaborate on the metabolic alterations in colonic epithelial cells, immune cells, and the gut microbiota during UC; and we discuss how these changes influence disease progression. Finally, we discuss potential therapeutic strategies targeting metabolic reprogramming for UC management. By integrating insights from macroepidemiology and micromolecular mechanisms, we delineate the association between metabolic reprogramming and UC and provide a valuable reference for future research into key mechanisms and novel treatment approaches.