Human Breast Milk as a Living Therapeutic System: Translational Implications for Neonatal Health

The use of human breast milk is gaining new recognition as more than just nutrition and as a multifaceted, dynamic, and biologically active environment with essential treatment effects in neonatal health. In addition to macronutrients, it has a variety of bioactive factors such as immunoglobulins, human milk oligosaccharides, antimicrobial peptides, cytokines, growth factors, microbiota, extra-cellular vesicles and microRNAs which, in combination, promote immune maturation, gut and brain development, metabolic programming and defense against infectious diseases and inflammatory diseases. This review summarizes the existing literature which conceives breast milk as a living therapeutic system with high level of translational application to the care of the neonatal population. We discuss mechanistic pathways by which breast milk has an impact on immune regulation, gut-microbiome interactions, neurodevelopment and long-term disease risk reduction, which are necrotizing enterocolitis, sepsis, allergic conditions, and metabolic disorders. New translational evidence that reveals the effects of breast milk-derived bioactive as natural immunomodulators, postbiotics, and epigenetic regulators is mentioned. The review also discusses clinical implications of vulnerable groups like preterm and low-birth-weight babies, as well as the issue of breast milk use, formula supplementation, and inequity in breastfeeding. This review brings together molecular biology, clinical neonatology, and translational nutrition science and emphasizes the importance of breast milk as a platform of early-life precision health and as a paradigm of the next generation of nutrition and therapeutic approaches.