D-allulose alleviates DSS-induced colitis via regulating gut microbiota and bile acid metabolism.

D-allulose is a rare monosaccharide with established safety and documented biological functions, whereas its potential effects on ulcerative colitis remains controversial. This study aimed to evaluate the impact of D-allulose on DSS-induced colitis and explore the underlying mechanisms. The results demonstrated that D-allulose supplementation (125, 250 and 500 mg/kg/day) significantly alleviated DSS-induced colitis symptoms, including body weight loss, colon shortening, diarrhea, and mucosal injury. D-allulose restored intestinal barrier integrity by upregulating tight junction proteins and mucins. Notably, D-allulose reduced neutrophil and macrophage infiltration and downregulated proinflammatory cytokines expression. Among the tested doses, the low dose of 125 mg/kg exhibited the most pronounced protective effect. Furthermore, low-dose D-allulose positively influenced the composition of colitis-associated microbiota, restoring gut microbiota homeostasis. Both untargeted and targeted metabolomic analyses demonstrated that D-allulose supplementation modulated bile acid metabolism, particularly by promoting the production of secondary bile acids (DCA and LCA) through the TGR5-PKA-NF-κB signaling pathway. Collectively, these results provided novel insights into the gut microbiota-metabolite-host crosstalk mediated by D-allulose and highlighted its potential as a functional food component for the management of colitis.