Metabolic disorders such as obesity and type 2 diabetes (T2D) represent a growing unmet clinical need. Accumulating evidence shows that the collection of microbes residing within the human intestinal tract influence host metabolism. Diet is one of the most important factors shaping the gut microbiome. So far, mainly microbial metabolism of dietary fibers has been studied, with less emphasis on dietary proteins. Here we will investigate how existing metagenome data available from different ethnicities is associated with different dietary patterns and test how they respond to diets high and low in proteins. Second, to clarify these responses in detail we will use bioreactors and investigate how microbiomes from patients and healthy controls respond to high/low protein diets as well as aromatic amino acids with the hypothesis that the microbiome produces bioactive compounds. We have identified one metabolite, imidazole propionate (ImP) from histidine, which is increased in blood of subjects with prediabetes and T2D. Further experiments have demonstrated that ImP can directly impair insulin sensitivity. Thus, we will investigate whether a low-protein diet (thus low in histidine) improves metabolism, alters the microbiota and reduces diabetogenic metabolites such as ImP in T2D patients of different ethnicities. Finally, we will confirm if the microbiome produces ImP in humans using isotope-labelled histidine.