Bovine milk osteopontin and B. infantis B8762 cooperatively restore gut homeostasis via host-microbe metabolic cross-talk

Abstract This study investigated the synergistic therapeutic effects of bovine milk osteopontin (lactopontin) and Bifidobacterium infantis B8762 in a murine model of infant gut barrier dysfunction. Lactopontin dose-dependently enhanced mucosal integrity, upregulated tight junction genes, elevated systemic protective metabolites (e.g., DHA), and restored Akkermansia muciniphila . Co-administration of lactopontin with the probiotic amplified these benefits, further enriching beneficial bacteria, suppressing E. coli , uniquely upregulating immunoregulatory genes ( Muc5b , Il10 ), and normalizing serum pro-inflammatory cytokines. The synergy operates via complementary mechanisms: lactopontin fortifies the physical barrier and metabolic defense, while the probiotic modulates mucosal immunity through tryptophan metabolism, leading to enhanced restoration of gut homeostasis. These findings offer mechanistic insights that could inform the development of targeted synbiotics for infant gut barrier dysfunction.