Curcumin alleviates DSS-induced ileal pouchitis in rats and is associated with suppression of JAK2/STAT3 signaling

Objective Curcumin shows therapeutic promise for pouchitis; however, its underlying mechanisms remain largely unexplored. This study aimed to elucidate the protective effects and mechanisms of curcumin against ileal pouchitis in a rat model. Methods A rat model of ileal pouchitis was established and randomized into three groups: Group A (control), Group B (pouchitis), and Group C (curcumin-treated). We assessed general health, histopathology, inflammatory cytokine levels, and intestinal barrier protein expression. Fecal microbiota was profiled using 16S rRNA sequencing, and untargeted metabolomics was employed to identify differential metabolites. Integrative analysis correlated microbiota and metabolite profiles. Furthermore, network pharmacology predicted hub genes and pathways, which were subsequently validated through in vivo experiments. Results DSS induction significantly increased pro-inflammatory cytokines, which were suppressed by curcumin treatment. Curcumin also upregulated the intestinal barrier protein occludin. Microbiota analysis revealed that curcumin restored microbial diversity and increased the abundance of short-chain fatty acid (SCFA)-producing beneficial bacteria. The microbial composition in the curcumin group (C) closely resembled that of the healthy control group (A). Metabolomic analysis identified phosphatidylcholine as a key differential metabolite elevated in the curcumin group. Network pharmacology identified STAT3 and JAK2 as central hub genes. Both mRNA and protein expression of STAT3 and JAK2 were significantly higher in the pouchitis group (B) compared to the control (A) and curcumin-treated (C) groups. Conclusion Curcumin significantly ameliorates DSS-induced pouchitis by restoring intestinal barrier integrity, reversing microbial dysbiosis, and correcting metabolic disturbances. Its therapeutic effect is primarily mediated through the inhibition of STAT3 phosphorylation and downregulation of the JAK2/STAT3 signaling pathway.