In this context, arterial hypertension and chronic kidney damage are of particular interest, as both diseases are associated with an increased cardiovascular risk. We combine different model systems with exploratory and interventional clinical trials to understand this interaction. We aim to use our findings to develop novel therapeutic approaches that reduce cardiovascular risk by modulating the bacteria-host interaction.
We are a translational research team consisting of clinician scientists, basic scientists and nutritionists and are located at the Experimental and Clinical Research Center (ECRC ). As a clinician scientist, Nicola Wilck combines his clinical work at the Division of Nephrology and Internal Intensive Care Medicine at the Charité-Universitätsmedizin Berlin with research at the ECRC.
As a junior research group we are funded by the Corona Foundation in the German Stifterverband. We are supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC Starting Grant).
Nicola Wilck, MD
Victoria McParland, PhD
Hendrik Bartolomaeus, MD
Ariana Rauch, M.Sc.
Strauss Lab, Experimental Ophtalmology, Charité CVK
Johannes Holle, MD
Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité CVK
Microbial dynamics in chronic kidney disease
In this project funded by the Corona Foundation (Corona-Stiftung im Deutschen Stifterverband) we aim to understand the role of the gut microbiota in mediating effects of chronic kidney disease (CKD) on cardiovascular disease (CVD). CKD and inflammation are known risk factors for CVD. The microbiota influences CKD and CVD as well as inflammation, and could be an important mechanistic link. In this project we aim to better understand the function and dynamics of the gut microbiota and associated immunophenotypes in patients with end-stage renal disease (ESRD). Using a multi-omics, translational approach we aim to better define the influence of the microbiome on CVD and to identify novel targets for the prevention and treatment of CVD in CKD. The focus of this project is 1) to better define the composition, function and the main influencing factors of the gut microbiome in ESRD over time and 2) to correlate microbiome composition and bacterial metabolites with immunophenotypes and clinical parameters. Additionally we aim to 3) identify potential microbiome-driven risk and protection patterns in ESRD patients and 4) quantify the contribution of the ESRD microbiome to CVD in experimental models.
In this ERC-funded project we investigate the relationship of nutrition, the gut microbiome and immune system in the context of arterial hypertension. Hypertension damages organs such as the kidney, thereby leading to premature death. Beyond elevated blood pressure, hypertension is characterized by a pro-inflammatory immune response ahead of measurable organ damage. Activated immune cells infiltrate the kidney to cause tissue injury. However, inflammation is insufficiently addressed by today’s drugs. Current treatments do not include the gut microbiota, its metabolites and the associated lymphoid tissue – the largest immune cell reservoir in the body. With our research we aim to characterize this missing link and move towards microbiota-based therapeutic strategies. We have recently shown for the first time that variations in dietary salt intake promote hypertension by modulating the immune system via the microbiota and its metabolites. Thus, the diet-microbiota axis is an important modulator of the immune response in hypertension. The vision behind Hyperbiota includes a personalized, microbiome-guided immunonutrition to reduce inflammation and modulate the immune response in such a way as to reduce organ damage associated with hypertension. By using an interdisciplinary approach, we will address the following: 1) the reciprocity of dietary composition, microbial community structure and metabolism, and immune response in hypertension in order to guide targeted interventions. 2) the changes in microbial ecology and immune cell homeostasis associated with worsening kidney function. 3) the extent to which the gut-associated lymphoid tissue contributes to the immune response in hypertension and its responsiveness to targeted interventions. 4) Knowledge gained in model systems will be translated and verified in mice associated with human microbial communities.