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 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).

The following data sets were generated

Article and author information

Author details

  1. Rozlyn CT Boutin

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    For correspondence
    rozlyn.boutin@msl.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1598-0104
  2. Charisse Petersen

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Sarah E Woodward

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6688-0595
  4. Antonio Serapio-Palacios

    Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Tahereh Bozorgmehr

    Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Rachelle Loo

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Alina Chalanuchpong

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Mihai Cirstea

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4900-6385
  9. Bernard Lo

    The Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Kelsey E Huus

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Weronika Barcik

    Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  12. Meghan B Azad

    Children's Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada
    Competing interests
    The authors declare that no competing interests exist.
  13. Allan B Becker

    Children's Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada
    Competing interests
    The authors declare that no competing interests exist.
  14. Piush J Mandhane

    Department of Pediatrics, School of Public Health, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  15. Theo J Moraes

    The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  16. Malcolm R Sears

    Department of Medicine, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  17. Padmaja Subbarao

    The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  18. Kelly M McNagny

    Department of Biomedical Engineering, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4737-3499
  19. Stuart E Turvey

    Department of Pediatrics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  20. Brett Finlay

    Michael Smith Laboratories, Microbiology & Immunology, University of British Columbia, Vancouver, Canada
    For correspondence
    bfinlay@msl.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5303-6128

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.

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

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.

Version history

  1. Received: February 21, 2021
  2. Accepted: April 7, 2021
  3. Accepted Manuscript published: April 20, 2021 (version 1)
  4. Version of Record published: April 26, 2021 (version 2)
  5. Version of Record updated: April 27, 2021 (version 3)

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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  1. Rozlyn CT Boutin
  2. Charisse Petersen
  3. Sarah E Woodward
  4. Antonio Serapio-Palacios
  5. Tahereh Bozorgmehr
  6. Rachelle Loo
  7. Alina Chalanuchpong
  8. Mihai Cirstea
  9. Bernard Lo
  10. Kelsey E Huus
  11. Weronika Barcik
  12. Meghan B Azad
  13. Allan B Becker
  14. Piush J Mandhane
  15. Theo J Moraes
  16. Malcolm R Sears
  17. Padmaja Subbarao
  18. Kelly M McNagny
  19. Stuart E Turvey
  20. Brett Finlay
(2021)
Bacterial-fungal interactions in the neonatal gut influence asthma outcomes later in life
eLife 10:e67740.
https://doi.org/10.7554/eLife.67740

Share this article

https://doi.org/10.7554/eLife.67740

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