A Water-Soluble Curcumin Glycoside Exhibits Superior Anti-Colitic Efficacy over Native Curcumin in DSS-Induced Colitis through Anti-Inflammatory Activity and Gut Microbiota Modulation.

Curcumin is a hydrophobic polyphenol with diverse biological activities; however, its practical application is limited by poor water solubility and low oral bioavailability. In this study, we investigated whether TSP, a previously developed water-soluble curcumin-stevioside glycoside, exerts superior anti-colitic efficacy compared with native curcumin. In LPS-stimulated macrophages, TSP more effectively suppressed IL-6 and TNF-α production than curcumin under aqueous conditions, indicating greater anti-inflammatory activity in a physiologically relevant environment. In a dextran sulfate sodium (DSS)-induced mouse colitis model, oral administration of TSP ameliorated disease severity more effectively than native curcumin administered at an equivalent curcumin dose, as evidenced by reduced body weight loss, preservation of colon length, improved histopathological features, and restoration of intestinal barrier integrity. TSP also was associated with altered gut microbial diversity and composition relative to the DSS group, including enrichment of short-chain fatty acid (SCFA)-associated taxa, particularly Akkermansia. Consistent with these compositional changes, functional prediction analysis revealed an increased abundance of microbial genetic pathways associated with SCFA biosynthesis in the TSP-treated group. Collectively, these findings demonstrate that TSP exerts superior anti-colitic effects relative to native curcumin, likely owing to its improved aqueous solubility and the resulting enhancement of curcumin availability under physiological conditions. The protective effects of TSP appear to involve both direct suppression of inflammatory responses and microbiota-mediated support of intestinal barrier homeostasis. These results highlight TSP as a promising curcumin-based candidate for functional food or adjunct therapeutic applications in inflammatory bowel disease.