Multiomics Analysis of Bacteroides cellulosilyticus Anticolitis via Gut Microbiota Metabolite-Mediated PI3K-Akt Signaling Pathway

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation and dysbiosis of the gut microbiota. Bacteroides cellulosilyticus (B. cellulosilyticus) is a multifunctional carbohydrate-degrading bacterium that may serve as a probiotic to enhance gut health by regulating gut microbiota. However, its specific role and mechanisms in UC remain unclear. This study utilized a population cohort and combined microbiome, metabolome, and transcriptome analyses to explore the therapeutic effects and potential mechanisms of B. cellulosilyticus on dextran sulfate sodium (DSS)-induced colitis in mice. After B. cellulosilyticus treatment, mice exhibited a 10.3% increase in body weight recovery (p < 0.01), a 12.9% reduction in disease activity index (DAI) scores (p < 0.05), and significant decreases in pro-inflammatory cytokine levels, including a 21.9% drop in IL-6 and a 24.6% reduction in TNF-α (p < 0.05; p < 0.0001). Notably, B. cellulosilyticus significantly inhibited the PI3K/Akt signaling pathway by effectively reducing the phosphorylation levels of both PI3K and Akt proteins. Additionally, metabolomic analysis revealed that B. cellulosilyticus significantly affected the gut metabolic profile. It led to increased levels of metabolites related to gut health, such as hypoxanthine. These metabolic changes were closely associated with the improvement of the microbial community composition. B. cellulosilyticus effectively restored microbial diversity and abundance in DSS-induced colitis. The integrated analysis of multiple omics approaches indicates that B. cellulosilyticus has the potential to serve as a probiotic therapeutic agent for UC. It offers new dietary and therapeutic strategies for managing UC by regulating the gut microbiota, altering metabolic profiles, and downregulating the PI3K-Akt signaling pathway.