The early-life gut microbiome establishes and matures sequentially during infancy and early childhood. Most important determinants for the microbiota development are the initial seeding at birth, mode of delivery, antibiotic use and nutrition. Considering the influence of nutrition in early life microbiome development, human milk oligosaccharides (HMOs) are key nutrients in breast milk which modulates the microbiome. Clinical observational studies with breastfed infants suggest that specific HMOs may help to prevent allergy onset through their action through the early life microbiome and respiratory infection. A RCT with formula fed infants suggests that 2FL and LNnT help to protect from lower respiratory tract infections and antibiotic use, probably thought their effects on the early microbiome maturation and activity.