Microbiota-Microglia Interactions in Pediatric Inflammatory Bowel Disease
Aperçu du projet
Despite the recent advances in our understanding between the connection between the microbes living in the gut and our mental health, there remains a wide knowledge gap in understanding how the brain is negatively impacted in disorders with inflammation of the gut. This is particularly important in the case of childhood gut disorders, which could negatively impact the developing brain and cause long-term behavioural impairments. We propose to study how disruption of gut-brain communication during development can lead to mental health problems in pediatric Inflammatory Bowel Disease (IBD). IBD is diagnosed in about 25% of patients during childhood and results in chronic gut inflammation and changes to gut microbes. IBD is also associated with increased risk for mental health problems including cognitive problems, anxiety and depression. It is not well understood how gut inflammation and brain dysfunction are connected, although interactions between the gut microbes and brain are critical for proper brain development. We propose that the microbes in the gut send signals to immune cells in the brain, but IBD disrupts these signals, changing brain development and ultimately leading to impaired mental health. To test this idea, we have developed and will characterize a unique mouse model of pediatric IBD which involves transplants of human patient gut microbes into mice. We can then directly test how these microbes contribute to altered brain development and behaviour. We can further identify metabolites released by gut microbes that may communicate directly with the brain. Finally, we will treat our mouse model with the missing microbe metabolites and look for improvements in brain function and behaviour. Overall, our results will accelerate the understanding of how the microbiome contributions to pediatric IBD and identify new therapeutic options for treating mental health issues in gut disorders.
Chef d'équipe
Annie Ciernia , University of British Columbia
Partenaire et Donateurs
Azrieli Foundation