Probiotic Therapy with Lactobacillus Restores Gut Microbiota and Modulates Immunity in Salmonella-Infected Mice

Salmonella typhimurium (S. typhimurium) is a major foodborne pathogen with a significant public health impact. Meanwhile, Probiotics have recently gained attention for their safe and effective role in managing gastrointestinal disorders. This study evaluated the effects of a probiotic mixture (Lactobacillus acidophilus and Lactobacillus plantarum) on gut immunity and dysbiosis in mice infected with S. typhimurium. Mice were randomly assigned to four groups (n = 3 per group): (1) Healthy control (CNG); (2) Infected control (CPG); (3) Probiotics only (LAPG); (4) Probiotics + infected (LAPST). Probiotics-treated mice showed improved clinical outcomes and reduced fecal Salmonella load (p < 0.0001). Alpha and beta diversity analyses showed significant microbial composition differences between groups. Firmicutes were the most affected phyla, followed by Proteobacteria and Bacteroidetes. Infected mice (CPG) showed decreased Patescibacteria and Actinobacteria, while probiotic treatment (LAPST) restored their levels. Linear Discriminant Analysis Effect Size showed LAPST enriched beneficial genera (e.g., Lactobacillus murinus, Streptococcus, Candidatus Arthromitus) associated with gut homeostasis, bacteriocin production, metabolism, immunity, and intestinal barrier integrity. Real-time quantitative PCR results showed that probiotic supplementation downregulated pro-inflammatory and upregulated the anti-inflammatory cytokines (p ≤ 0.05). Additionally, it modulated genes involved in apoptosis, tight junctions, and oxidative stress. These findings provide mechanistic insight and may have translational relevance for managing Salmonella-induced gut disorders in livestock.