3-Fucosyllactose alleviates DSS-induced mouse colitis through modulation of the PI3K-Akt signaling pathway: An integrated multi-omics analysis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by colonic inflammation, intestinal barrier disruption, and dysbiosis of gut microbiota. This study investigates the beneficial effects of 3-fucosyllactose (3-FL), an important human milk oligosaccharide (HMO), on a murine model of dextran sulfate sodium (DSS)-induced colitis. To elucidate the underlying mechanisms, we employed a multi-omics approach integrating transcriptomics, metabolomics, and microbiomics. Transcriptomic analyses show that 3-FL modulates the PI3KAkt signaling pathway, critical for regulating cellular responses to inflammation. Metabolomic profiling reveals changes in metabolites linked to inflammation, while microbiomic assessments indicate restructuring of gut microbial composition after 3-FL treatment. The integrated analysis reveals that 3-FL exerts anti-inflammatory effects through modulation of the PI3K-Akt signaling pathway mediated by gut microbiota-derived metabolites. Collectively, these findings underscore the potential of 3-FL as a prebiotic therapeutic agent for UC, highlighting its multifaceted mechanisms of action through modulation of gut microbiota.