Probiotic potential of Companilactobacillus alimentarius Y4 in alleviating ciprofloxacin-resistant Salmonella-induced intestinal inflammation through microbiota–metabolite modulation

Abstract The emergence of ciprofloxacin-resistant Salmonella poses a significant challenge to antimicrobial therapy. Probiotics that inhibit ciprofloxacin-resistant Salmonella offer a safer alternative with fewer side effects than conventional antibiotics. In this study, a strain of Companilactobacillus alimentarius Y4, isolated from kimchi, exhibited strong antibacterial activity against Salmonella C1, Escherichia coli, and other intestinal pathogens. Biological characterization showed that C. alimentarius Y4 maintained a relative growth rate of 80% at pH 3.0 and 87.13% in the presence of 0.3% bile salts. It retained over 98.8% antibacterial activity even after exposure to pepsin, trypsin, protease K, and catalase. Additionally, C. alimentarius Y4 downregulated the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), while upregulating the anti-inflammatory cytokine IL-10, which may contribute to alleviating intestinal injury induced by ciprofloxacin-resistant Salmonella C1. Gut microbiota analysis revealed that C. alimentarius Y4 colonized the intestine and increased the abundance of beneficial gut microbes, including Lachnospiraceae bacterium COE1 and Muribaculaceae bacterium CAG-485. Metabolomic profiling further indicated that C. alimentarius Y4 upregulated metabolites such as L-leucine, L-lysine, and tryptophan, contributing to the restoration of intestinal metabolic balance. Collectively, C. alimentarius Y4 may mitigate intestinal inflammation by regulating cytokine expression, repairing mucosal damage, rebalancing gut microbiota composition, and restoring metabolic homeostasis. These findings indicate that C. alimentarius Y4 may contribute to alleviating intestinal inflammatory damage caused by multidrug-resistant Salmonella infection, suggesting its potential as a promising probiotic candidate.