Project 451914

Asthma is the most common chronic disease of childhood and its incidence in Canada has doubled in only 25 years. Although familial history can be a predictor of asthma, it fails to explain this sudden increase. In contrast, environmental factors such as growing up on a farm, vaginal birth, breastfeeding, household pets, and lack of antibiotic use in infancy have been associated with a lower asthma risk, and may better explain its sharp increase in incidence. The nature of these exposures leads to changes in our intestinal microbes (also known as the gut microbiome), and it is now hypothesized that changes in the gut microbiome early in life may lead to asthma development. We have produced significant work supporting this hypothesis, providing evidence for an early window in life, during which changes to our gut microbiome can have profound and long-lasting effects in the immune system and subsequent risk of asthma. However, very little is known about the specific microbes that lead these changes. We propose to study this currently unexplored connections following up previous results from our lab, revealing that gut microbes, and fungi in particular, can increase asthma risk by modifying specific immune cell types. We will expand these observations by experimenting in mice that are colonized with defined collections of microorganisms, providing a controlled approach to truly define the role of fungi in asthma development. This approach will expand our knowledge on the role that microbes have on the mechanisms that lead to asthma, and has great potential to identify asthma preventative strategies for future clinical investigation.