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

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 Pichia kudriavzevii 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 P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii 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.

Automated summary

This study found that overgrowth of the fungus Pichia kudriavzevii in the infant gut increases the risk of asthma, demonstrating a causal association between early-life fungal dysbiosis and later allergic airway disease. The research also showed that the growth and adherence of P. kudriavzevii in the gut epithelial cells are altered by short-chain fatty acids, suggesting potential for microbiota-based asthma therapeutics leveraging inter-kingdom interactions.