Grant: Canada Postdoctoral Research Award (CPRA) program

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, affects millions of people worldwide. People living with IBD experience ongoing gut inflammation, which often leads to abdominal pain, diarrhea, and bleeding, reducing an individual's quality of life. One key feature of IBD is a "leaky gut", where the normal barrier that separates gut bacteria from the rest of the body becomes weakened. When this barrier is disrupted, bacteria and their products leak out of the gut, causing inflammation and worsening symptoms. Unfortunately, we do not fully understand what initially weakens this barrier. Patients with IBD tend to have an imbalance of proteases, i.e., enzymes that break down proteins in our gut to help our body function properly. Some gut bacteria also produce proteases, and recent studies now link specific bacteria to IBD. This suggests a potential connection between the proteases released by these bacteria and the barrier disruption seen in IBD. In this project, we will use cutting-edge models that mimic the human gut, including patient-derived "mini-guts". By investigating the link between bacterial proteases and the breakdown of the gut barrier, we aim to uncover the underlying causes of leaky gut. We will translate our findings in preclinical models to determine how changes in gut leakiness induced by proteases lead to IBD. This research will improve our understanding of how bacteria contribute to IBD and identify new therapeutic targets. By focusing on bacterial proteases, we hope to find ways to protect the intestinal barrier, facilitate gut healing, reduce symptoms, and improve the quality of life for people living with IBD.