In this WP we will validate novel (dietary) metabolites and proteins found in pour revious FMT studies (Kootte, Cell metabolism 2017 and de Groot, Gut 2019) as involved in metabolic control and epigenetic modulation. In collaboration with Radboud UMC (prof Netea and prof Riksen) we aim to further characterize the biological activity of these metabolites in vitro epigenetic changes in myeloid cells and investigate how metabolites elicit the epigenetic changes, and which beneficial microbes induce these and affect the (innate) immune system. Finally, we will perform a large (dietary) intervention study aimed at affecting specific metabolic (aromatic) metabolite production to decrease surrogate markers of CVD risk. At the end of this grant, we strive to have identified consortia of beneficial bacterial strains that can be used in humans for therapy. Moreover, we have elucidated of the effect of our novel identified microbial derived metabolites on trained immunity and have substantiated to in vivo kinetics with isotope labeled aromatic amino acids
