Salmonella Typhimurium disrupts intestinal homeostasis by inducing inflammation and metabolic dysregulation during infection. Although probiotic-mediated protection against Salmonella infection has been widely reported, the underlying host-targeted mechanisms remain incompletely understood. Here, we investigated the protective effects of wild badger-derived Lactiplantibacillus plantarum Y40 against S. Typhimurium SL1344 infection in mice, focusing on host metabolic regulation. We found that Y40 pretreatment significantly alleviated infection-induced colonic inflammation and epithelial barrier disruption. Transcriptomic analysis revealed that SL1344 infection induced an immune-dominant transcriptional profile, characterized by activation of inflammatory pathways and suppression of metabolic processes, particularly fatty acid metabolism. In contrast, Y40 pretreatment reprogrammed host gene expression by attenuating inflammatory responses while restoring metabolic pathways. Targeted serum fatty acid profiling demonstrated that Y40 reversed infection-induced reductions in serum free fatty acids and normalized fatty acid composition, including restoration of oleic acid (C18:1N9C) and linoleic acid (C18:2N6). Mechanistically, Y40 upregulated peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream targets (FASN, ACC1, and SCD1), which were suppressed by SL1344 infection. Pharmacological inhibition of PPARγ in MC38 cells abolished the protective effects of Y40. Collectively, these findings establish that L. plantarum Y40 protects against Salmonella infection by activating PPARγ-dependent fatty acid metabolism, thereby maintaining intestinal barrier integrity and limiting inflammation.
Gu et al. (Wed,) studied this question.