Implementation of human milk antimicrobial peptides for immune protection in formula feeding

Human milk is widely recognized as the biological standard for early-life nutrition, providing both essential nutrients and bioactive components that support immune development. However, breastfeeding is not always feasible, and infant formula remains a necessary alternative in specific clinical and social contexts. Despite advances in formulation, significant immunological differences persist between breastfed and formula-fed infants, contributing to the so-called “immunological gap.” This review critically examines the potential of human milk-derived antimicrobial peptides (HM-AMPs) as functional ingredients to partially address this gap. Current evidence indicates that these peptides, derived from proteins such as lactoferrin, caseins, and α-lactalbumin, exhibit antimicrobial and immunomodulatory activities through mechanisms including membrane disruption and modulation of inflammatory pathways. However, most available data are derived from in vitro and preclinical models, limiting direct translation to clinical outcomes. In addition, significant challenges remain, including peptide instability during industrial processing, uncertain bioavailability in the gastrointestinal tract, and limited clinical validation. While emerging computational and bioengineering strategies offer opportunities to optimize peptide functionality, their large-scale implementation remains constrained by technological and regulatory factors. Overall, HM-AMPs represent a promising but still developing approach to improving infant formula functionality. Their contribution should be interpreted as partial and context-dependent, rather than as a complete replication of the immunological properties of human milk.