The Role of Antimicrobial Peptides in Primary Sclerosing Cholangitis

• Applicant: Dr. Igor Spivak
• Subject Area: Gastroenterology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445667004

Background: Primary sclerosing cholangitis (PSC) is a disease of an undefined etiology, however it has been highly associated with inflammatory bowel diseases and consistent microbiome alterations. Several studies have linked antimicrobial peptides (AMPs) with the composition and function of the intestinal microbiome. Yet human studies transcending beyond the microbiome composition to its function are scarce and studies involving AMP signatures in PSC are hitherto non-existent. Aims: In a comprehensive multi-omic characterization and data analysis of patients with ulcerative colitis, with and without PSC, and of healthy controls we will identify differences between the microbial patterns between the different groups. We aim at developing a human-based pipeline for comprehensive AMP quantification in feces and along the GI tract: After a “bottom-up”-approach to identify peptides of interest the Parallel Reaction Monitoring (PRM) – technique will be applied to yield quantitative data. Through a bioinformatics analysis where the microbiome, AMP and gut transcriptome data from patients and controls are integrated we hope to characterize PSC-specific AMP signatures and their impact on microbiome assembly and function. Being able to identify AMPs that are enriched or depleted in the GI tract of patients with PSC we’ll administer or downregulate them in animal models of the disease and examine whether they exacerbate or alleviate its phenotype, respectively, potentially introducing novel therapeutic opportunities.

• DFG Programme: WBP Fellowship
• International Connection: Israel
• Host: Professor Dr. Eran Elinav