Contribution of the microbiome to asthma risk in premature infants

Premature infants are at increased risk of life-long diseases and treatments. Among the most compromised organs of premature infants are the lungs. In Canada and globally, very premature infants (between 28-32 weeks of gestation) and extremely premature infants (less than 28 weeks of gestation) are up to three and four times respectively, more likely to develop recurrent wheeze than term infants. Until now, lung compromise has been an accepted result of developmental delay and lung structural damage caused by medical practices needed to support respiration. However, epidemiological evidence shows that infants who do not develop lung structural damage are nevertheless at increased risk of asthma, indicating that other variables impact this risk. Exciting recent findings from infant studies and animal models implicate the large community of microbes (microbiome) in the human gut as a factor that contributes to asthma. However, despite their heightened risk of asthma and the pronounced microbiome alterations linked to prematurity, no clinical study of the microbiome and asthma has studied premature infants. Leveraging a world class team of microbiome experts and an established cohort specifically designed to capture clinical and environmental exposures unique to the NICU, this team grant will be the first to unravel microbiome-asthma linkages in the highly vulnerable premature infant population. We will apply powerful statistical tools to detect independent associations between microbiome features and asthma risk, and to interrogate the capacity of these species to mediate asthma risk. We will then use animal models to define the mechanisms by which specific microbes contribute to immune and neuroimmune pathways that lead to allergic airway inflammation. Our work will culminate in the identification of pre-clinical microbiome-based therapeutics aimed at decreasing the risk of asthma in thousands of Canadian children born prematurely every year.