Grant: Operating Grant: SickKids-CIHR-IHDCYH New Investigator Grants

Asthma is an incurable inflammatory disease of the lungs that usually develops during childhood. In Canada, asthma incidence has quadrupled in the past 20 years, without a known cause. We, and others, have provided important evidence that implicates the large community of microbes that reside in the gastrointestinal tract of infants, also known as the early-life gut microbiome. Our recent human and mouse data indicates that fungal overgrowth during antibiotic treatment exacerbates early-life atopic immune responses. Thus, our goal now is to further study the currently unexplored role of gut fungal dysbiosis during early life immune development, and to explore strategies to control fungal overgrowth during infant antibiotic use. This is important because antibiotics are given empirically to young infants and often cannot be avoided in this vulnerable population. This proposal is framed around a translational approach, in which information obtained from infant clinical studies has been used to design experiments in animal models. These experiments will provide important mechanistic insight about the immune consequences of early life fungal overgrowth, as well microbiome-based strategies to prevent immune regulation that lead to asthma development. Given that the lung inflammatory response in an asthma murine model has been repeatedly shown to be responsive to early life modulation of the gut microbes, this approach has great potential to identify currently unknown microbial taxa and immune interactions relevant in asthma pathogenesis. This will significantly expand our knowledge on the microbiome-derived signals that drive immune dysregulation beyond bacteria, and may also identify therapeutics aimed at preventing this epidemic disease.