Deciphering Microbiome, Transcriptome, and Metabolic Interactions in the Presence of Probiotic against Typhimurium in a Murine Model.

Typhimurium (. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of ( 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with . Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with but not infected (LAG); and a group fed with and challenged with (LAST). The results revealed a reduction in levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of was found to downregulate pro-inflammatory cytokine mRNA induced by while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-β) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with promotes the growth of beneficial commensal genera while mitigating -induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism.