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

Elife. 2021 Apr 20:10:e67740. doi: 10.7554/eLife.67740.

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 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.

Keywords: asthma; human; immunology; inflammation; medicine; microbiota; mouse; mycobiota; pichia kudriavzevii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / microbiology*
  • Bacteria
  • Bacterial Physiological Phenomena
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Infant
  • Mice
  • Mice, Inbred C57BL
  • Pichia / physiology*
  • Specific Pathogen-Free Organisms

Supplementary concepts

  • Pichia kudriavzevii

Associated data

  • SRA/PRJNA624902