Grant: Operating Grant - PA: Reproductive and Child Heath (start-up grants)

A large proportion of Canadian infants are exposed to antibiotics in early life. Although critical for treating some bacterial infections, epidemiological evidence has indicated that 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, therefore, disrupting this important process. When this occurs in early life it may be an important driver of immunologic and metabolic diseases later in life, such as inflammatory bowel diseases, 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. We have developed a piglet model to test the relationship between early life antibiotic exposure and metabolic disruption later in life and have found that antibiotic treated pigs are less able to tolerate a glucose meal. We now aim to explore the mechanism through which this occurs, so as to develop strategies to prevent the deleterious effects of early life antibiotic exposure on metabolic disease.