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

越来越多的证据表明，肠道细菌群，即所谓的肠道微生物组，在心血管和心脏代谢性疾病的发展中起着重要作用。通过元基因组学和代谢组学相结合的方法，已确定与肠道微生物区系相关的不同代谢物在宿主中具有系统效应。其中一种代谢物是咪唑-丙酸酯(IMP)，它是通过肠道微生物处理氨基酸组氨酸而产生的。最近，弗雷德里克·贝克赫德教授的S团队发现，糖尿病患者的肠道中产生的IMP越来越多，并导致肝脏和肌肉中胰岛素信号的受损。最近在心力衰竭患者中进行的病例对照研究的结果也表明，IMP水平升高的心力衰竭患者可能与IMP相关。然而，IMP是否在心力衰竭的发生和发展中起因果作用尚不清楚。本项目的目的是在实验性心力衰竭模型中研究肠道微生物区系相关代谢产物IMP对心脏不良重构的影响。研究结果可能有助于更好地了解肠道微生物群与心力衰竭的发展之间的相互作用，并可能有助于开发以肠道微生物群为靶点的潜在心力衰竭预防和治疗策略。

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.