Exploring the impact of bacterial membrane vesicles on cholestatic liver diseases

• Applicant: Professorin Dr. Claudia Günther
• Subject Area: Gastroenterology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 542876266

Immune-mediated inflammatory diseases (IMIDs) such as inflammatory bowel disease (IBD) and autoimmune liver disease (Primary sclerosing cholangitis [PSC]) are complex, multifactorial disorders characterized by progressive inflammation, driven by tissue damage and consecutive dysfunction of the affected organs. Although etiology remains largely unknown, they share a common underlying predisposition and pathogenic features. Emerging evidence indicates that not only IBD but also PSC is characterized by alterations in gut microbial and metabolite composition and that translocation of these factors across a disrupted intestinal barrier may contribute to the pathogenesis of PSC. However, the gut microbiota not only negatively influences immune- and metabolically-driven diseases, but also provides essential health benefits to its host, particularly by regulating immune homeostasis. Accordingly, there is a growing awareness of the need to improve our causal understanding of molecular mechanisms by which bacteria elicit their beneficial or pathogenic effects on individual host cells and how microbiome-immune interaction influences organ function and pathology. Within this project, we will dissect microbiota-gut-liver communication via bacterial-derived extracellular vesicles and determine how this interaction affects liver inflammation and fibrosis and PSC-related autoimmunity. The long-term vision of this project is to identify novel routes of microbiota-liver crosstalk that can be targeted for therapeutic approaches.

• DFG Programme: Research Grants