Bacterial–fungal interactions in the neonatal gut influence asthma outcomes later in life

Abstract

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast <i>Pichia kudriavzevii</i> in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of <i>P. kudriavzevii</i> within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that <i>P. kudriavzevii</i> growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics.