Lacticaseibacillus rhamnosus D1 Fermented Milk Confers Protection Against Typhoid Fever Through Immunomodulation and Gut Microbiota Regulation in Mice

This study investigated the protective effect of fermented milk by <i>Lacticaseibacillus rhamnosus</i> D1 in a murine model of Typhoid fever, focusing on cytokines, antimicrobial peptides and microbiota modulation. BALB/c mice were pre-treated with milk fermented by <i>L. rhamnosus</i> D1 prior to <i>Salmonella</i> Typhimurium challenge. Outcomes assessed included survival, weight change, bacterial translocation, mRNA expression of cytokines and antimicrobial peptides, in addition to gut microbiota modulation. Mice receiving fermented milk exhibited higher survival rates, reduced bacterial translocation and attenuated weight loss compared to controls. mRNA expression analyses revealed that <i>L. rhamnosus</i> D1 pre-treatment suppressed the expression of pro-inflammatory cytokines (IFN-γ, IL-6 and IL-12) and upregulated anti-inflammatory cytokines (IL-5, IL-10 and TGF-β), as well as antimicrobial peptides (Reg3β, Reg3γ and Lcn2). Furthermore, we observed that the consumption of fermented milk changed the gut microbiota of infected mice, not only by modulating the existing taxa, but also by facilitating the emergence of unique, potentially beneficial microbial lineages, such as <i>Muribaculum</i>, <i>Roseburia</i>, <i>Intestinimonas</i>, <i>Bdellovibrio</i> and <i>Facklamia</i>. These findings indicate that <i>L. rhamnosus</i> D1 protected mice against <i>S.</i> Typhimurium infection through immunomodulatory and microbiota-mediated mechanisms, changing mucosal immunity and strengthening the intestinal barrier by modulating gut microbiota and immune responses, in addition to promoting host antimicrobial defenses.