Antibiotic-induced Malassezia expansion in the infant gut promotes early-life immune dysregulation and airway inflammation in mice

Antibiotics have deleterious consequences for the gut microbiome and can increase the risk of childhood asthma. While the effects of antibiotics on the bacterial microbiome and asthma risk are well characterized, their impact on the fungal microbiome (mycobiome) remains vastly unexplored. We investigated the effect of antibiotic use on the gut mycobiome in an observational, prospective clinical study of young infants. Antibiotic treatment resulted in increased fungal abundance and expansion of the yeast Malassezia spp. in the infant mycobiome. Based on these findings, we colonized germ-free mouse pups with a defined consortium of mouse-derived bacteria (Oligo-MM12) with or without Malassezia restricta. Colonization with this yeast increased myeloid and lymphoid intestinal immune responses deemed critical in atopy development, and elevated airway inflammation in house-dust mite (HDM)-challenged mice and respiratory syncytial virus (RSV)-infected mice. Further evaluation in eosinophil-deficient mice revealed that the observed immune response is partially dependent on this cell type. This translational work demonstrates that expansion of Malassezia spp. is a previously overlooked collateral effect of infant antibiotic use, which may offer a potential strategy to prevent or mitigate pediatric asthma and related conditions.