Strain-Specific Immunomodulation by Bifidobacterium longum
Probiotic bacteria exhibit strain-specific immunomodulatory effects, yet how such functional heterogeneity translates into distinct disease outcomes remains incompletely understood. Here, we compared two Bifidobacterium longum strains isolated from healthy Korean individuals. In vitro co-culture assays identified SNUG50527 and KBL3109 as strains with contrasting cytokine profiles, which were subsequently validated in vivo. Oral administration of SNUG50527 to healthy mice induced innate and adaptive immune activation, characterized by increased intestinal expression of Ifng, Tnf, Il17a, and Reg3g and reduced PD-L1 expression on dendritic cells, whereas KBL3109 suppressed T cell activation and Il4 expression. In disease models, SNUG50527 reduced tumor growth in MC38 tumor-bearing mice by promoting infiltration of CD4+ and CD8+ T cells and IFN-? production. In contrast, KBL3109 alleviated DSS-induced colitis by reducing inflammatory cytokines and increasing Zo1 expression. Microbiome and targeted metabolite profiling showed strain-associated alterations in gut microbiota composition and metabolite profiles, including short-chain fatty acids, bile acids, and amino acids. Comparative genomic and CAZyme analyses indicated that SNUG50527 harbored host glycan-associated CAZyme families, whereas KBL3109 exhibited a broader repertoire of complex polysaccharide-associated enzymes, suggesting differential adaptation. These findings suggest that strain-level immune profiling can distinguish functionally divergent B. longum strains and link strain-specific microbial features with distinct disease-related phenotypes.
Probiotic bacteria exhibit strain-specific immunomodulatory effects, yet how such functional heterogeneity translates into distinct disease outcomes remains incompletely understood. Here, we compared two Bifidobacterium longum strains isolated from healthy Korean individuals. In vitro co-culture assays identified SNUG50527 and KBL3109 as strains with contrasting cytokine profiles, which were subsequently validated in vivo. Oral administration of SNUG50527 to healthy mice induced innate and adaptive immune activation, characterized by increased intestinal expression of Ifng, Tnf, Il17a, and Reg3g and reduced PD-L1 expression on dendritic cells, whereas KBL3109 suppressed T cell activation and Il4 expression. In disease models, SNUG50527 reduced tumor growth in MC38 tumor-bearing mice by promoting infiltration of CD4+ and CD8+ T cells and IFN-? production. In contrast, KBL3109 alleviated DSS-induced colitis by reducing inflammatory cytokines and increasing Zo1 expression. Microbiome and targeted metabolite profiling showed strain-associated alterations in gut microbiota composition and metabolite profiles, including short-chain fatty acids, bile acids, and amino acids. Comparative genomic and CAZyme analyses indicated that SNUG50527 harbored host glycan-associated CAZyme families, whereas KBL3109 exhibited a broader repertoire of complex polysaccharide-associated enzymes, suggesting differential adaptation. These findings suggest that strain-level immune profiling can distinguish functionally divergent B. longum strains and link strain-specific microbial features with distinct disease-related phenotypes.