Coordination Funds

• Applicant: Professor Dr. Christoph Schramm
• Subject Area: Gastroenterology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 278045702

Primary Sclerosing Cholangitis (PSC) is a relatively rare, chronic progressive disease of bile ducts which leads to liver cirrhosis and cholangiocarcinoma. To date there is no effective therapy to alter the progressive course of disease. Patient survival is limited by the high risk of cirrhosis as well as hepatobiliary malignancy, but in addition health related quality of life is often impaired by PSC-associated complications such as osteoporosis.PSC is characterized by inflammation and fibrosis of intra- and/or extrahepatic bile ducts and by its strong association with inflammatory bowel disease, most often PSC-asssociated pancolitis. These disease features underline the importance of the mucosal surface for disease pathogenesis. In recent years it has become clear that the microbiome is critical for the maintenance and breach of mucosal immune homeostasis. Within the CRU306 we hypothesize that the microbiome and its associated immunological and metabolic changes determine disease pathogenesis and course. In previous work we could show that PSC is associated with changes in intestinal microbiota composition, which were validated across geographical regions, and recently also with changes in the biliary microbiota. We have shown that PSC is associated with altered immune cell populations in blood and liver and that T cells from patients with PSC showed increased pro-inflammatory cytokine production after stimulation with heat-inactivated bacteria. The CRU brings together a number of clinical and basic science experts in hepatology, immunology, microbiome research and bioinformatics. In the next funding period we will focus on the functional meaning of the observed changes in PSC-associated microbiota, immunological and metabolic patterns with regard to disease pathogenesis, phenotype and disease course in humans and respective mouse models.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 306: Primär Sklerosierende Cholangitis