The Impact of the gut microbiota-dependent metabolite imidazole propionate on the progression of heart failure

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Accumulating evidence suggest a contributory role of intestinal bacterial flora, the so-called gut microbiome, for the development of cardiovascular and cardiometabolic diseases. By means of combined metagenomic and metabolomic approaches distinct gut microbiota-related related metabolites have been identified with systemic effects in the host. One of these metabolites is Imidazole-Propionate (ImP) which is produced upon gut microbial processing of the amino acid histidine. Recently, Prof. Fredrik Bäckhed´s group found that ImP is increasingly produced in the intestine of diabetic patients and contributes to impaired insulin signaling in the liver and muscle. Findings from recent case-control studies in patients with heart failure also point to a putative clinical relevance of ImP in heart failure patients with elevated ImP levels. However, it is unclear whether ImP plays a causal role in the development and progression of heart failure. The aim of the current project is to investigate the impact of the gut microbiota-related metabolite ImP on adverse cardiac remodeling in an experimental heart failure model. The findings of the investigations may add to a better understanding of the interaction between the gut microbiome and the development of heart failure and may contribute to the development of potential preventive and therapeutic strategies for the treatment of heart failure by targeting the gut microbiome.