Breast milk–saliva interactions in shaping early mucosal immunity

The neonatal period is characterized by immunological immaturity, rendering newborns vulnerable to infections at mucosal surfaces such as the oral and gastrointestinal tracts. Breast milk, traditionally recognized for its nutritional and immunological roles, and neonatal saliva, once considered a passive secretion, interact biochemically to create a synergistic defense system. These interactions include the xanthine oxidase-lactoperoxidase system, which generates hydrogen peroxide and hypothiocyanite, compounds with potent antimicrobial and immunomodulatory properties. Beyond immediate antimicrobial action, these factors regulate mucosal barrier integrity, immune gene expression, and glycosylation processes. This review integrates recent findings on the compositional elements, biochemical pathways, and immunological outcomes of breast milk-saliva interactions, emphasizing their roles in shaping early mucosal immunity, establishing beneficial microbiota, and promoting immune tolerance. These insights also highlight potential strategies to enhance artificial infant formulas and therapeutic interventions for neonatal care.