A10 - Connecting the gut microbiota to the cardiorenal axis in HFpEF

Chronic kidney disease (CKD) may contribute to the development of HFpEF, but the underlying mechanisms are poorly understood. The subproject investigates the importance of CKD-associated microbiota and microbial metabolites for inflammation and cardiac remodelling. In order to specifically investigate the role of the microbiota and its metabolites, we use in particular gnotobiotic mouse models, microbiota transfers and metabolite treatments. Thus, this subproject will make an important contribution to the understanding of the heart-kidney axis and mechanistically investigate the role of the microbiome as a link between these important organs in HFpEF.

Graphical Abstract: CKD promotes HFpEF via microbiota-dependent mechanisms. We hypothesize that microbiota-dependent mechanisms may partly mediate the reno-cardiac interaction in HFpEF as an intermediate link  between the kidney and the heart. CKD is characterized by a marked intestinal dysbiosis and an accumulation of certain bacterial metabolites with a resulting toxic effect. Metabolite imbalance in CKD promotes inflammation and pro- inflammatory immune phenotypes. Moreover, dysbiosis promotes gastrointestinal barrier dysfunction and pro-inflammatory mechanisms that could contribute additionally to HFpEF. We aim to better understand inter-organ crosstalk in  HFpEF and CKD in order to establish the microbiota as a therapeutic target in HFpEF.