The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysbiosis of intestinal microbes and an aberrant immune response against members of the microbiome. First-degree relatives (FDR) often share risk factors with IBD patients, such as an increased intestinal permeability and sero-positivity for several anti-microbial antibodies, leading to an enhanced risk to develop IBD during their life time (Keita et al., 2018 & Vermeire et al., 2001). It was found that, disease progression evolves over time and that shifted patterns of gut microbiome correlates with disease status (Gevers et al., 2014). However, these patterns are inconsistent among published studies, since most patients are already treated with drugs that might also affect the growth of common gut microbes (Maier et al., 2018). In this project we are focusing on early microbiome changes and the resulting impact on the immune response in patients at high risk for IBDs, i.e. FDRs and treatment naïve early disease patients.
This is a project within the DFG Research Unit RU5042 miTarget.
In this project we will analyse the T cell reactivity of FDRs and treatment naïve early disease patients against candidate microbes identified in previous and ongoing studies. For that purpose we will carry out T cell reactivity screenings against identified colitogenic microbes and other potential antigens using our established antigen-reactive T cell enrichment (ARTE) technology in order to characterise the responsive disease-relevant T cell populations. The overall aim is to find a direct link between microbial dysbiosis and aberrant immune reaction, and to identify biomarkers and antigens that help to predict and explain the clinical onset and disease course of IBD.