Impact of microbiome-derived metabolites on innate immunity, immune function and tissue homeostasis in graft-versus-host disease (P05)

• Subject Area: Hematology, Oncology ; Immunology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 395357507

Besides bacteria, microbiota-derived metabolites play a pivotal role in modulating innate and T cell mediated immunity in graft-versus-host disease (GvHD). In fecal samples of allo-SCT recipients, we identified a microbiome signature consisting of bacteria and their associated immunomodulatory metabolites that associate with clinical outcomes and can engage a specific innate immune pathway to mediate protection from GvHD. Led by these discoveries, we will investigate the microbiota/metabolomic profile in intestinal tissue samples of patients with or without GvHD (Aim 1), analyze the functional role of identified metabolites/consortia on GvHD (Aim 2) and test the influence of metabolite cocktails or bacterial consortia on human GvHD in preclinical model systems (Aim 3). Our goal is to develop microbial-based interventions that minimize GvHD for more effective cancer treatment.

• 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. Hendrik Poeck; Professor Dr. Jürgen Ruland