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

eLife

Allan B Becker¹  Meghan B Azad¹  Kelly M McNagny²  Malcolm R Sears³  Bernard Lo⁴  Stuart E Turvey⁵  Alina Chalanuchpong⁶  Kelsey E Huus⁶  Sarah E Woodward⁶  Rachelle Loo⁶  Rozlyn CT Boutin⁶  Mihai Cirstea⁶  B Brett Finlay⁷  Piush J Mandhane⁸  Antonio Serapio-Palacios⁹  Tahereh Bozorgmehr⁹  Charisse Petersen⁹  Weronika Barcik⁹  Theo J Moraes^1,10  Padmaja Subbarao^1,11 

[1] Children’s Hospital Research Institute of Manitoba and Department of Pediatrics and Child Health, University of Manitoba, WinnipegMB, Canada;Department of Biomedical Engineering, University of British Columbia, Vancouver, Canada;Department of Medical Genetics University of British Columbia, Vancouver, Canada;Department of Medicine, McMaster University, Hamilton, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Department of Pediatrics, University of British Columbia, Vancouver, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Michael Smith Laboratories, University of British Columbia, Vancouver, Canada;Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada;Michael Smith Laboratories, University of British Columbia, Vancouver, Canada;Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada;Department of Pediatrics, University of Alberta, Edmonton, Canada;School of Public Health, University of Alberta, Edmonton, Canada;Michael Smith Laboratories, University of British Columbia, Vancouver, Canada;The Hospital for Sick Children, Toronto, Canada;The Hospital for Sick Children, Toronto, Canada;Department of Pediatrics, University of Toronto, Toronto, Canada;

关键词: pichia kudriavzevii;    microbiota;    asthma;    mycobiota;    Human;    Mouse;    Other;   

DOI  :  10.7554/eLife.67740

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY