A novel Curcuma wenyujin-derived fructan modulates gut microbiota and metabolic pathways to ameliorate DSS-induced colitis.

Ulcerative colitis (UC) involves epithelial barrier breakdown, dysregulated mucosal immunity, and dysbiosis of the gut microbiota (GM). Given the biotherapeutic potential of dietary fructans, this study aimed to isolate a neutral fructan (CWP-W-1) from Curcuma wenyujin and to characterize its chemical structure and anti-colitis effects. CWP-W-1 was purified by DEAE-Sepharose and gel-filtration chromatography. Its structure was established using HPGPC, monosaccharide profiling, FT-IR, GC-MS, and NMR. In a DSS-induced UC mouse model, CWP-W-1 treatment alleviated disease severity and weight loss, decreased the disease activity index and rectal bleeding, prevented colon shortening, and restored histological architecture, with increased goblet cells and mucin staining. Metagenomic sequencing showed that CWP-W-1 mitigated DSS-associated dysbiosis, recovering α-diversity and shifting β-diversity toward healthy controls, with decreases in Proteobacteria and enrichment of beneficial taxa. Metabolite analyses indicated that CWP-W-1 increased short-chain fatty acids (SCFAs) and remodeled the tryptophan metabolic pathway, shifting the pro-inflammatory kynurenine bias toward indole-derived aryl hydrocarbon receptor (AhR) ligands, consistent with epithelial barrier support and immune homeostasis. Collectively, these results demonstrated that CWP-W-1 was a structurally defined fructan with significant therapeutic potential for UC through coordinated modulation of barrier function, mucosal immunity, and the gut microbiota.