Grant: Project Grant

Inflammatory bowel diseases (IBD) are chronic, debilitating illnesses. The goal of treatment in IBD is complete healing of intestinal inflammation. Despite achieving this goal, up to 60% of IBD patients suffer with chronic abdominal pain, which is a devastating outcome. Although females are predominantly affected, the sex-specific causes of pain are not well understood, because most pre-clinical studies use only male mice. Previous studies have shown that gut microbes play an important role in pain signalling. Using a mouse model of IBD in remission, we found that female mice had increased pain compared to males. Females also had different gut bacteria and distinct bacterial-derived products, compared to males. When we transplanted stool from female mice with IBD in remission to germ-free males and females, both sexes developed pain. However, when we transplanted stool from male mice with IBD in remission to germ-free males and females, only male mice developed pain. This suggests that there is something unique about gut microbes in females, either the microbes themselves or the products they make, that is "pro-pain" when compared to males. The goal of our research is to study how gut microbes play a sex-specific role in the development of chronic pain in IBD. We will study whether male and female sex hormones change gut bacteria and bacterial-derived products in a mouse model of IBD in remission. We will examine how these gut bacteria modify pain signalling by performing stool transplants and studying how bacterial-derived products change the activity of male and female pain-sensing nerves. Our research may have a broad impact on the health of patients suffering from IBD as it will give us a greater understanding into the sex-specific role of gut microbes in pain sensation. This may lead to unique sex-specific strategies to treat pain in IBD, such as the use of stool transplants or targeted therapies against specific microbes or microbial products.