Probiotic supplementation promotes bone development, immune maturation, and cognitive function in growing mice

BACKGROUND: Early life is a critical window for bone mineral deposition, immune system development, and neurodevelopment. This study evaluated the effects of four probiotic strains on bone growth and regulation of immune function and cognitive function using a growing mouse model, thereby providing preclinical evidence for potential applications in supporting infant and child health. RESULTS: colony-forming units of four probiotic strains or saline from postnatal week 1 to week 5. At the experimental endpoint, bone microarchitecture was evaluated using micro-computed tomography and histomorphometric analysis. Lacticaseibacillus paracasei L578 increased femoral length and bone volume fraction, while Bifidobacterium bifidum B11 supplementation specifically improved cortical bone parameters. Mechanistic insights revealed that L. paracasei L578 upregulated serum concentrations of bone formation markers, namely osteocalcin, bone-specific alkaline phosphatase, and procollagen type I N-terminal propeptide, along with the transcription levels of key osteogenic transcription factors Bmp2, Runx2, and Osterix, which constitute a hierarchical cascade governing osteoblast lineage commitment and differentiation. Immunological assessments indicated that both L. paracasei L578 and B. animalis subsp. lactis BAL531 significantly increased colonic concentrations of immunoglobulin A, immunoglobulin G, and interferon-γ, suggesting their role in regulating the Th1/Th2 immune balance and promoting mucosal humoral immunity. In behavioral tests, L. paracasei L578 administration resulted in significantly longer time spent in the central area of the open field and a higher spontaneous alternation rate in the Y maze, indicating enhanced cognitive function. CONCLUSION: Collectively, these findings suggest that L. paracasei L578 enhances bone formation metabolism, stimulates longitudinal bone growth, increases bone mass, regulates mucosal humoral immunity, and improves cognitive function, positioning it as a promising probiotic for supporting development.