Role of gut dysbiosis and microbial metabolites in the pathogenesis and progression of heartfailure

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Heart failure (HF) is currently regarded as a multisystem disorder, and chronic inflammation has been hypothesized as a major contributing factor. Alterations in gut microbial composition (“gut dysbiosis”), and translocation of microbial toxins/metabolites to the bloodstream, have recently been associated with HF pathogenesis. Hence, the concept of modulating gut microbial composition with the goal of reducing systemic inflammation thereby ameliorating HF progression has generated broad interest in the scientific community. However, several challenges remain, as the core microbiota linked to HF are not universally established yet due to so far typically small monocentric studies with heterogeneous methodology. Moreover, a systematic correlation of microbiome and metabolome as the resulting phenotypic readout is missing in HF. Thus, there is an urgent need to constitute larger patient cohorts to establish a core gut microbiome in HF patients. THFs would allow to dissect whether there is a universal correlation between gut microbiome and the pathogenesis of HF, putting forward the “gut hypothesis” of HF. In the proposed project, based on our own preliminary data, we hypothesize that a maladaptive composition of the gut microbiome exists that may have a relevant impact on the pathogenesis and progression of heart failure. Moreover, specific features of the gut microbiota and its blood-detectable metabolites could potentially represent clinically useful biomarkers for the prognosis and prevention of heart failure. We believe that comprehensive mechanistic studies such as the one proposed here are needed to identify the direct effects of altered gut microbiota on HF and to unravel the associated pathomechanisms. In addition, analysis of experimental mouse models of gut dysbiosis and patient cohorts may allow us to identify initial approaches to improved therapy and prevention.