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 PI3K-Akt 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. Mechanism diagram of the anti-colitis effect of 3-FL. • 3-Fucosyllactose (3-FL) shows prebiotic potential for colitis. • 3-FL reduces inflammation via PI3K-Akt. • 3-FL treatment enhances gut microbiota diversity and metabolite profiles. • 3-FL boosts gut microbiota and metabolites.