Microbial triggers of intestinal inflammation in hosts deficient in X-linked inhibitor of apoptosis protein (P02)

• Subject Area: Gastroenterology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 395357507

Altered host-microbial interactions are a hallmark of inflammatory bowel disease (IBD) and will be investigated in P02 through the study of XIAP deficiency, one of the most common Mendelian forms of IBD. In the first funding period, we could demonstrate that human and murine XIAP deficiency is associated with Paneth and myeloid cell defects. These defects promote susceptibility to microbiota-dependent intestinal inflammation. In the second funding period, we will study host and microbial molecular requirements for intestinal inflammation in XIAP deficiency, will develop protective bacterial consortia for the prevention and treatment of intestinal inflammation, and will identify microbial triggers of disease in human IBD patients with XIAP mutations through fecal microbiome transfer into germfree mice. The overall goal of this project is to identify therapeutically targetable pathogenic host-microbiome interactions in IBD.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1371: Microbiome Signatures -- Functional Relevance in the Digestive Tract
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professor Dr. Philipp Jost, until 9/2020; Dr. Monica Yabal; Professor Dr. Sebastian Zeissig