Grant: Catalyst Grant: Environments, Genes and Chronic Disease

A large proportion of Canadian infants are exposed to antibiotics in early life. Although critical for treating some bacterial infections, antibiotic exposure during the early developmental period is associated with an increased risk of obesity later in life. There is an abundant population of microbes colonizing the gut that play an important role in shaping human development. Antibiotic exposure alters the composition and diversity of these microbes; when this occurs in early life it may be an important driver of immunologic and metabolic diseases later in life, including inflammatory bowel disease, asthma, diabetes and obesity. Because the effect of antibiotics on longterm obesity outcome are only seen when administered in the early life we believe that a programming effect, in the form of epigenetic modifications, is responsible. Epigenetic modifications are alterations to the DNA that change the expression of genes without changing the underlying DNA sequence. In some regions, nearly a third of children receive antibiotics in the first 6 months of life, therefore it is critical that we gain an understanding of the impacts of this environmental exposure on long-term chronic disease. The contribution of neonatal antibiotics and resulting changes in the microbiome to diabetes and obesity later in life has not been experimentally tested. We will use the piglet as a model for the human infant to identify how postnatal antibiotic exposure influences immune and pancreas development that program an infant for an increased risk of obesity and insulin resistance later in life.