Project 466949

The prevalence of inflammatory bowel disease (IBD) and other chronic disorders of the gut have increased more than 50% since 2010 in Canada and there is currently no cure. Over 25% of people with IBD are diagnosed during childhood and many of these patients develop anxiety, depression and cognitive impairments that persist into adulthood. How early life gut inflammation impairs brain function in children remains understudied, however, animal models provide insight into the underlying mechanisms of IBD and may lead to novel therapeutic development.Intestinal inflammation alters compositions of microbiota (microorganisms like fungi and bacteria) in the gut. Interestingly, gut microbiota produce metabolite molecules that signal to immune cells in the brain called microglia. I hypothesize that an altered composition of gut microbiota in children with IBD changes metabolite signaling to microglia and consequently impairs mental health.My proposed project will develop the first mouse model of juvenile IBD that captures the whole gut-to-brain-to-behaviour spectrum of the disorder. I will then use this model to determine the role of microglia in pediatric IBD. Gut inflammation will be chemically induced in juvenile mice and then the impact on gut microbiota composition, microglia functioning, and behavioural development will be assessed. The long-term goal of this work is to identify how disorders like pediatric IBD lead to life-long impacts on the brain and increased prevalence of psychiatric disorders. The microbiota is an exciting target for personalized medicine as microbiome manipulations are a feasible early intervention. By developing better therapies for pediatric IBD, we aim to mitigate negative impacts on brain development and improve patient quality of life.