Bacterial-fungal interactions in the neonatal gut influence asthma outcomes later in life
- University of British Columbia, Canada
- University of Manitoba, Canada
- University of Alberta, Canada
- The Hospital for Sick Children, Canada
- McMaster University, Canada
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.
Data availability
Data Availability: All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data have been deposited in the NCBI SRA under accession code SUB7276684 (https://www.ncbi.nlm.nih.gov/sra/PRJNA624902).
Article and author information
Author details
Funding
Canadian Institutes of Health Research (Project Grant PJT-148484)
- Brett Finlay
Canadian Institutes of Health Research (Foundation Grant FDN-159935)
- Brett Finlay
AllerGen (12CHILD)
- Meghan B Azad
- Allan B Becker
- Piush J Mandhane
- Theo J Moraes
- Malcolm R Sears
- Padmaja Subbarao
- Stuart E Turvey
- Brett Finlay
Canadian Institutes of Health Research (Doctoral: Vanier Canada Graduate Scholarships)
- Rozlyn CT Boutin
Vancouver Coastal Health-Canadian Institutes of Health Research (UBC MD/PhD Studentship Award)
- Rozlyn CT Boutin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were in accordance with the University of British Columbia Animal Care Committee guidelines and approved by the UBC Animal Care Committee (protocols A17-0322 and A13-0344).
Human subjects: The CHILD Cohort Study protocols were approved by the human clinical research ethics boards at all universities and institutions directly involved with the CHILD cohort (McMaster University, University of British Columbia, the Hospital for Sick Children, University of Manitoba, and University of Alberta). Work in the Finlay/Turvey labs is conducted under the ethics certificate number H07-03120.
Copyright
© 2021, Boutin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bacterial-fungal interactions in the neonatal gut influence asthma outcomes later in life
eLife 10:e67740.
https://doi.org/10.7554/eLife.67740
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