Grant: Project Grant

Ulcerative colitis (UC) is a chronic disease affecting the gut with limited treatments and significant risk of needing surgery to remove the large bowel (colon). It is very concerning that we still don't know what causes UC, especially since it is becoming more common, particularly in children in Canada. Microbes (mostly bacteria) are different in UC but we don't know if they cause the disease or are changed because of the inflammation found in UC. We have recently shown that children with UC have different bacteria in the healthy-appearing small bowel; we have also developed and just published a new method to isolate bacteria that might be virulent (disease causing) by utilizing the patient's immune system to trap bacteria and identified how they might do this. The next step is to combine these findings and find bacteria that might be causing or at least driving damage in UC. To do this we will also take advantage of some of the basic and unexplained features of UC: 1. It only involves the colon; 2. It is a continuous disease; 3. The appendix seems to have an important (but not understood) role. This study will build on these interesting observations to test our hypothesis that bacteria (and molecules/products they make) from unaffected areas travel down the bowel and cause the damage seen in UC. We will test this by collecting samples from different parts of the bowel in children just diagnosed with UC during a colonoscopy test. Three large Canadian centers, that are already working together through a funded National Network, will collect samples during colonoscopy to identify these bacteria. We will find the bacteria that travel down to the sick areas and identify those that can penetrate and injure the bowel and those that activate the immune system. We will then confirm that these bacteria indeed cause damage using cell models and germ-free mice. This will help explain what causes UC and will direct new therapies.