Grant: Project Grant

Asthma is a chronic inflammatory disease of the airways currently affecting more than 300 million people worldwide. It is now the most common childhood disease in Western countries. Asthma has a genetic component, but genetics offers only a partial explanation for the dramatic rise in prevalence over the last five decades. Accumulating evidence points to environmental factors as key contributors. One such factor is the microbiome, the collection of microorganisms that inhabit our body. Using stool samples collected from children enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, we recently demonstrated a connection between gut microbiome alterations in the first 100 days of life and an increased risk to develop asthma. We also found that low levels of specific intestinal bacteria in asthmatic children are linked to low levels of microbial products (metabolites) known to regulate essential immune functions. However, the immune status of those children was not determined, and the mechanisms by which an altered microbiome and metabolites functionally link to asthma is unknown. Based on the role of the immune system in asthma, we hypothesize that specific changes in the gut microbiome contribute to the development of childhood asthma by producing metabolites that modulate the host immune response. We will test this hypothesis as follows. First, we will leverage the CHILD cohort to study the immune and metabolic signatures that correlate with clinical asthma. Second, we will determine the interrelationships among the infant gut microbiome, microbial metabolites, immune system status, and asthma. Third, we will validate those interrelationships in a mouse model of asthma. This project will provide important new understanding of how asthma develops, and it will identify ways that we might prevent or treat asthma, potentially using probiotics.