AbstractBackgroundStaphylococcus aureusis a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carryS. aureusasymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influenceS. aureusacquisition and retention in early life.ResultsWe recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, particularly within the first 2 months. It is weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns ofS. aureuscarriage, positively associated withAcinetobacterspecies,Streptococcus parasanguinis,Streptococcus salivarius, andVeillonellaspecies and inversely associated with maternalDolosigranulum pigrum. Furthermore, we identify a gene family, likely acting as a taxonomic marker for an unclassified species, that is significantly anti-correlated withS. aureusin infants and mothers. In gene content-based strain profiling, infantS. aureusstrains are more similar to maternal strains.ConclusionsThis improved understanding ofS. aureuscolonization is an important first step toward the development of novel, ecological therapies for controllingS. aureuscarriage.