Lacticaseibacillus paracasei 18 effectively ameliorates dextran sodium sulfate-induced colitis in mice through...

Ulcerative colitis (UC) is a persistent inflammatory bowel disorder marked by mucosal inflammation and dysbiosis of the gut microbiome. Lacticaseibacillus paracasei 18 (LP18) is a versatile carbohydrate-degrading bacteria that may work as a probiotic to improve gut health by modulating gut microbiota. However, its exact function and mechanisms in UC remain ambiguous. This research employed integrated microbiome, metabolome, and transcriptome analysis to investigate the therapeutic benefits and underlying mechanisms of Lacticaseibacillus paracasei on dextran sulfate sodium (DSS)-induced colitis in murine models. After the intervention of LP18, colitis mice demonstrated an improvement in body weight loss and a mitigation of colonic shortening, accompanied by a moderate increase of expressions in colonic tight junction-related genes (Claudin-1, Claudin-2, Claudin-5, ZO-1, and Occludin). Additionally, LP18 improved the structure and diversity of the gut microbiota in these DSS-induced mice. Metabolomic study suggested that LP18 substantially influenced the intestinal metabolic profile, particularly compounds associated with tryptophan metabolism. The metabolic alterations were closely linked to the enhancement of the microbial community makeup. The analysis of colon RNA sequencing indicated that, in comparison to the DSS group, LP18 significantly downregulated various immune-related signaling pathways, especially the PI3K/AKT/NF-κB pathways. Correlation analysis of microbiota, metabolism, and genes uncovered a substantial association between the taxa enhanced by LP18 and the critical genes in the NF-κB signaling pathways. Overall, the integrated analysis of multiple omics approaches revealed that LP18 may function as a probiotic therapeutic agent for UC. It represents novel dietary and therapeutic strategies for controlling UC through the regulation of gut microbiota, modification of metabolic profiles, reinforcement of the intestinal barrier, and downregulation of the PI3K/AKT/NF-κB signaling pathway.