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

肠道微生物群依赖性代谢物丙酸咪唑对心力衰竭进展的影响

• 批准号: 436269184
• 负责人: Privatdozent Dr. Arash Haghikia
• 金额: --
• 依托单位: Department of Molecular and Clinical Medicine
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/436269184?language=en
• 关键词: Impact; gut; microbiota; dependent; metabolite

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.

越来越多的证据表明，肠道细菌菌群，即所谓的肠道微生物群，在心血管和心血管代谢疾病的发展中起着重要作用。通过宏基因组学和代谢组学相结合的方法，已经确定了不同的肠道微生物群相关代谢物在宿主体内具有全身作用。其中一种代谢物是咪唑丙酸酯（ImP），它是由肠道微生物处理氨基酸组氨酸产生的。最近，Fredrik教授Bäckhed的研究小组发现，糖尿病患者的肠道中ImP的产生越来越多，并导致肝脏和肌肉中的胰岛素信号受损。最近心衰患者病例对照研究的结果也指出ImP在ImP水平升高的心衰患者中可能具有临床相关性。然而，目前尚不清楚ImP是否在心力衰竭的发生和进展中起因果作用。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群相关代谢物ImP对不良心脏重构的影响。这些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发展之间的相互作用，并可能有助于开发针对肠道微生物群治疗心力衰竭的潜在预防和治疗策略。