Project 460732

Inflammatory bowel disease (IBD) is a chronic, relapsing condition that affects the intestinal tract. Canada has one of the highest frequencies of IBD world-wide, imposing a tremendous burden to our health care system in direct ($1.28 billion per year) and indirect costs ($1.3 billion) such as loss of productivity. The causes of IBD are unknown but involve a combination of genetic and environmental factors that include diet. The biggest recent increase in IBD globally has occurred in Asia and the Middle East, likely due to westernization of their traditional diets. It is also believed that changes in the population of bacteria that inhabit our gut (collectively called "microbiome") play a role in driving gut inflammation in IBD. These bacteria share our diet that in turn modifies bacterial behaviour. Thus, we believe that certain components of our diet, such as a high salt diet, can influence bacterial behaviour to produce chemicals that trigger or drive inflammatory responses in the gut. We discovered that the microbiome from healthy people at risk for IBD who go on to develop the disease several years later, harbour microbes that produce molecules called "proteases" that cause inflammation. Individuals with active IBD also harbour these protease-producing bacteria. We suspect that dietary components may promote these pro-inflammatory bacterial functions as we have recently found that high salt diet, which is characteristic of processed foods in the Western diet, increases proteolytic activity in the gut microbiome of mice colonized with IBD bacteria. This proposal will therefore explore the link between a high salt diet, bacterial inflammatory proteases and will test a novel and safe therapy using specific probiotics that inhibit the proteolytic activity. The knowledge gained will support the development of new treatments through a new generation of designer probiotics or dietary modification, to prevent and cure IBD.