Lacto-N-Triose II Alleviates DSS-Induced Colitis via Gut Microbiota and Metabolites Associated with the PI3K-Akt Pathway

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by intestinal barrier dysfunction, immune dysregulation, and gut microbiota dysbiosis. This study examined the therapeutic potential of lacto-N-triose II (LNT II), a core component of human milk oligosaccharides, in colitis. Results showed LNT II significantly alleviated disease pathology, restored epithelial barrier integrity, and modulated inflammatory responses. It reversed colitis-induced microbial dysbiosis and altered key metabolites such as D-xylulosonic acid, Sakacin P, and taurocholic acid. Transcriptomic analysis revealed LNT II suppresses inflammation via the PI3K-Akt signaling pathway. Integrated multiomics analysis established a complete mechanistic cascade: LNT II remodels gut microbiota, regulates specific metabolites, and inhibits the PI3K-Akt pathway to alleviate colitis. These findings provide comprehensive experimental evidence supporting LNT II as a novel prebiotic therapy for UC, demonstrating its efficacy through systematic regulation of the microbiota-metabolite-immune network.