The microbes living in our gut have recently been found to affect important developmental processes such as brain development and hormonal regulation during puberty. Microbes produce compounds that affect the brain, as well as change the activity of sex hormones. Despite these recent advances, there remains a wide knowledge gap in understanding how the brain and puberty onset are negatively impacted in disorders with inflammation of the gut. This is particularly important in the case of childhood gut disorders, which could negatively impact development and cause long-term behavioural impairments.
We propose to study how problems in the gut can confuse signals to the brain, affecting children’s growth and mental health 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 and is correlated with delayed puberty. It is not well understood how gut inflammation, brain dysfunction and puberty are connected, although the presence of specific gut microbes is critical for proper development. We found that IBD disrupts microbes that produce compounds that support brain development and hormone regulation.
To test how this happens, 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 puberty. We can further identify chemicals released by gut microbes that may communicate directly with the brain or sex organs. Overall, our results will help us learn about how gut health affects children’s brains and growth, leading to better treatments for improving mental health and developmental outcomes for children with IBD.
