Stachyose attenuates DSS-induced colitis and is associated with elevated colonic medium-chain fatty acids: an integrated multi-omics analysis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, immune dysregulation, and gut microbiota dysbiosis. Using a dextran sulfate sodium (DSS) mouse model, we applied an integrated multi-omics approach comprising untargeted metabolomics, colonic transcriptomics, and 16S rRNA sequencing to evaluate the effects of the prebiotic stachyose (STA). STA supplementation alleviated colitis and coincided with marked increases in several medium-chain fatty acids (MCFAs), including azelaic acid and 3-hydroxyoctanoic acid. Transcriptomic profiling revealed modulation of fatty acid metabolism genes (e.g., Mfsd2a, Anxa1) and enrichment of pathways such as PPAR signaling and fatty acid degradation. Microbiota analyses showed enrichment of Ruminiclostridium_9, Roseburia, and Christensenellaceae, with partial restoration of microbial diversity and functions. Integrated correlations linked specific taxa, MCFAs, and host lipid-related genes. While associative and requiring mechanistic validation, these findings suggest colonic MCFAs as candidate mediators of the protective effects of STA in experimental colitis.