Host and microbial mechanisms in PSC-IBD
Research type
Research Study
Full title
A systems biology approach for identification of host and microbial mechanisms and druggable targets for the treatment of PSC-IBD
IRAS ID
299706
Contact name
Mohammed Nabil Quraishi
Contact email
Sponsor organisation
University Hospitals Birmingham
Duration of Study in the UK
1 years, 9 months, 5 days
Research summary
Primary sclerosing cholangitis (PSC) is a chronic liver disease of an unknown cause and with no effective medical treatment. Nearly three-quarters of people with a chronic liver disease called primary sclerosing cholangitis (PSC) have a form of inflammatory bowel disease (PSC-IBD). Patients with PSC-IBD appear to be at greater risk of colon cancer and need for bowel surgery. We recently discovered that the bacteria attached to the bowel in patients with PSC-IBD were very different to those with UC and healthy individuals. These bacteria had genes that were associated with converting bile acids into a form that can be absorbed into the colonic tissue. Consistently analyses of genes obtained from biopsies of the colon from patients with PSC-IBD suggested that the pathways that control the levels of bile acid in the colon were in a state of overdrive. These novel findings raised several important questions in helping us understand reasons for the onset of PSC and PSC-IBD and if these distinctions in the gut bacteria have anything to do with it. Interestingly an oral antibiotic called oral vancomycin has been shown to improve both the liver tests and colonic inflammation in patients with PSC-IBD. This antibiotic does not get absorbed so is its mode of action is possibly due to a change in the gut bacteria.
In this proposed study, we will recruit fifteen PSC-IBD who are undergoing a colonoscopy as part of standard of care. If they have colonic inflammation then participants will be given 4 weeks of treatment with oral vancomycin, and stool samples and colonic biopsies will be collected at different timepoints We will evaluate changes in the gut bacteria, the chemicals it produces, bile acids and genes being expressed within the bowel in order to identify specific disease pathways that are associated with PSC-IBD.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
21/WM/0197
Date of REC Opinion
16 Sep 2021
REC opinion
Further Information Favourable Opinion