Insights into the Impact of Bifidobacterium bifidum, B. breve, and B. longum on the Immune Response Against Salmonella Infection in Neonatal Rats

Infants exhibit diminished susceptibility to external infections, a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract. Nonetheless, a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages. In this study, the impact of early intervention with Bifidobacterium bifidum (B. bifidum), B. breve, and B. longum on neonatal rats infected with Salmonella enterica serovar Typhimurium (S. typhimurium) SL1344 were compared. The study encompasses various immunity levels, including gut immunity, central immunity (thymus), peripheral immunity (spleen), and brain immunity. Following Salmonella infection, significant alterations in neonatal rats were observed in growth and developmental levels, immune markers, cytokine levels, balance of T lymphocyte subpopulations, intestinal barrier function, and blood-brain barrier integrity. Compared with B. breve and B. longum, B. bifidum demonstrated more pronounced efficacy in regulating these physiological processes. By conducting multi-level analyses of gut microbiota, bifidobacterial community, colonic content metabolomics, and serum metabolomics, the significance of B. bifidum's role is underscored, and the immune-enhancing function of messenger metabolites is unveiled. Among these metabolites, γ-L-Glutamyl-L-glutamic acid and Orotic acid were found to be shared by all three species, while Hippuric acid and 1a,1b-dihomo Prostaglandin F2α were unique to B. bifidum, and DL-Arginine was specific to B. longum. Overall, this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections, emphasizing the significant role of B. bifidum.