Human Milk Oligosaccharides: Shaping the Anti-Infective Status in Infancy

Human milk is widely recognised as the optimal source of nutrition for newborns and infants, providing not only an ideal macronutrient composition but also a range of bioactive components that exert important non-nutritional functions, and as such it represents the first functional food consumed in early life. Among these bioactive components, the human milk oligosaccharides (HMOs)-a structurally diverse family of glycans present in human milk at concentrations 100- to 1000-fold higher than in the milk of other mammalian species-have emerged as multifunctional contributors to the establishment of the intestinal microbiome, immune development, anti-infective defence, and epithelial barrier integrity during a developmental window characterised by immune immaturity. The aim of the present narrative review is to synthesise current evidence on the anti-infective properties of HMOs in infancy and to integrate, within a single framework, five interconnected mechanisms through which HMOs protect the infant against infection: glycan-mimicry-based competitive inhibition of pathogen adhesion, direct antimicrobial and antibiofilm activity, selective prebiotic shaping of the gut microbiome, modulation of innate and adaptive immune responses, and reinforcement of mucosal barrier integrity in the gut and lungs. Breastfeeding constitutes a natural strategy for anti-infective protection in early childhood, while infant formulas supplemented with biotechnologically produced HMOs that are structurally identical to those in human milk provide measurable benefits for non-breastfed infants.