Nanoformulated Curcumin Ameliorates Ulcerative Colitis via Gut Microbiota Modulation and Barrier Function Restoration

The gut microbiota is increasingly recognized as a key mediator of the anticolitis effects of curcumin (CUR). However, the clinical translation of this promising activity is severely hampered by CUR's low solubility and poor bioavailability. Although nanoencapsulation represents a promising strategy to address these limitations, the preventive effect of nanocurcumin (nano-CUR) against colitis remains largely unexplored. The present study aimed to elucidate the preventive effects of nano-CUR on intestinal barrier function, gut microbiota composition, and metabolic profiles in a murine model of dextran sulfate sodium (DSS)-induced colitis. The results demonstrated that pre-supplementation of nano-CUR significantly ameliorated disease severity, attenuated intestinal barrier disruption, and suppressed colonic inflammation in mice with DSS-induced colitis. Mechanistically, integrated 16S rRNA sequencing and untargeted metabolomics demonstrated that nano-CUR-restored microbial homeostasis and enhanced the production of short-chain fatty acids, linking microbial shifts to anti-inflammatory outcomes. Fecal microbiota transplantation (FMT) further validated the causal role of the nano-CUR-remodeled microbiota in conferring protection. Collectively, these findings decipher the mechanism by which nano-CUR interacts with the gut microbiota, confirming that dietary nano-CUR consumption protects against ulcerative colitis by modulating the gut microbiome and its metabolic output.