| Project Detail |
Boosting mucus secretion for inflammatory bowel disease remission
Under healthy conditions, the gut’s mucus layer acts as a barrier, keeping microbes away from direct contact with the intestinal cells and the immune system. However, in inflammatory bowel diseases (IBDs), this barrier is compromised, allowing microbes to penetrate the mucus layer and come into contact with the cells of the intestinal lining and the immune cells beneath it. This causes persistent inflammation and tissue damage, central to the symptoms and progression of IBD. The ERC-funded MucusIBD project utilises the discovery that inducing excess intestinal mucus secretion in mice protects against colitis. Researchers will test a bile acid in preclinical mouse models to induce mucus production and IBD remission.
Inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis, are chronic, debilitating conditions affecting millions worldwide. There is currently no cure for IBD, only treatments aimed at inducing long lasting remission. These treatment options act mainly by inhibiting the patient’s immune system, leaving patients immunocompromised, and come with a high annual direct cost. Even with advanced treatment, most IBD patients will require surgery during their lifetimes. Thus, more affordable treatment option which are not focused on immune suppression are needed.
While the etiology of IBDs is not clear, it is thought that breakdown of gut barrier function is a major driver of chronic intestinal inflammation. Indeed, penetrance of luminal microbes into the mucus layer which covers the intestinal epithelium is a hallmark of IBDs. This penetrance and contact of microbes with the host’s immune system drives a proinflammatory response and prevents tissue healing. While performing our ERC-funded research project we found a way to induce excess intestinal mucus secretion in mice. We found this excess mucus secretion protected mice from development of colitis in a model of IBD. We also uncovered the mechanism which controls intestinal mucus secretion and discovered a cheap and reproducible way to pharmacologically induce excess mucus secretion using a bile acid.
Our goal is to determine whether pharmacologically inducing intestinal mucus production in preclinical mouse models of IBD can induce and sustain remission. The projects methodology encompasses preclinical trials utilizing three distinct mouse models to rigorously test the efficacy and safety of our innovation. A comprehensive market analysis, informed by stakeholders including healthcare professionals and patient advocacy groups, will guide the development process, ensuring the therapeutic approach meets the real-world needs of IBD patients. |
