A SYSTEMS BIOLOGY APPROACH FOR IDENTIFICATION OF HOST AND MICROBIAL MECHANISMS AND DRUGGABLE TARGETS FOR THE TREATMENT OF PSC-IBD
|M. Nabil Quraishi
© M. Nabil Quraishi
Aim of research
Primary sclerosing cholangitis (PSC) is a rare hepatobiliary manifestation of Inflammatory Bowel Disease (IBD) that is associated with significant and disproportionate unmet needs and a higher all-cause mortality compared with IBD alone. Unfortunately, no medical therapy has been proven to slow disease progression in PSC-IBD, and liver transplantation is the only life-saving intervention for patients.
We recently identified distinct mucosal transcriptomic profiles in PSC-IBD with regard to bile acid metabolism, bile acid signalling and a central role of enteric dysbiosis. Data from other groups have shown that oral vancomycin attenuates colonic inflammation and improves biochemical markers of cholestasis in PSC. In our study, we hypothesise that oral vancomycin attenuates colonic mucosal inflammation in PSC-IBD by restoring gut microbiota-mediated bile acid homeostatic pathways. We aim to identify druggable gut microbial and host molecular pathways associated with bile acid-mediated colonic mucosal inflammation in PSC-IBD.