Harmonious Allies: The Synergy of Antimicrobial Proteins and Microbes in Breast Milk to Protect Neonatal Health

Breast milk is vital for infant survival, protecting against infections and strengthening the immune system. In addition to nutrients, breast milk contains beneficial microorganisms, antimicrobial peptides and proteins (APPs), including lactoferrin and lysozyme, and peptides such as defensins and cathelicidins that destroy harmful bacteria and regulate the neonatal immune response. Breast milk also promotes the growth of beneficial gut bacteria (Bacteroidaceae and Bifidobacteriaceae) while reducing harmful pathogens, fostering a healthy gut microbiome, and supporting long-term infant health. Traditionally, research on antimicrobial proteins and milk microbiota has been conducted in isolation. However, at the molecular level, these components do not function independently; they interact synergistically, influencing immunomodulation, inflammation, and the composition of the gut microbiome. Therefore, this review aims to provide an overview of the discovery and identification of APPs in breast milk, the dynamic relationship between the breast milk microbiota, and the potentiation of artificial feeding with supplemented formulas when breastfeeding is impossible, benefits on newborn immune systems, and even the benefits to breast tissue.