Association between uraemic toxins and the intestinal microbiome

Chronic kidney disease (CKD), which is more prevalent in women, and its high risk for cardiovascular disease (CVD) with nearly 50% of all deaths in CKD patients caused by CVD, is such a complex disease and its socio-economic burden is extremely high. This project will in this context focus on the gut-kidney axis and the role of the intestinal microbiome as important contributor to the genesis and evolution of CVD in CKD and as possible therapeutic target to improve outcome of CKD patients. For this purpose, microbiological culturing, fermentation, and bioinformatics approaches will be utilised in order to identify possible associations between specific bacterial members of intestinal microbiota in CKD patients and circulating (uraemic) metabolites (toxins). From the bioinformatics perspective, the impact of body fluid composition on microbiota will be studied in both data-driven and hypothesis- driven approaches. This will be coupled with validation of predicted associations and relationships using in vitro culture-based experiments. Therefore, the project will utilise a targeted isolation and anaerobic culturing of toxin-producing bacterial species from CKD faecal samples and co-culturing and metabolomic profiling of bacterial toxin-producers with their predicted positive/negative interacting species in a state-of-the-art parallelized microscale fermentation system. The outcome of this integrated bioinformatics and in vitro approach will yield a more profound understanding of the gut-kidney axis and identify possible routes for the testing and development of microbiome-based modulation strategies in CKD.