Tang W H Wilson, Kitai Takeshi, Hazen Stanley L
From the Department of Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T., S.L.H.); Department of Cardiovascular Medicine, Heart and Vascular Institute (W.H.W.T., T.K.); and Center for Clinical Genomics, Cleveland Clinic, Cleveland OH (W.H.W.T.).
Circ Res. 2017 Mar 31;120(7):1183-1196. doi: 10.1161/CIRCRESAHA.117.309715.
Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine -oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure-associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
近年来,人们对肠道微生物群与宿主的相互作用产生了浓厚兴趣,因为越来越多的证据表明,肠道微生物群在人类健康和疾病(包括心血管疾病)中发挥着重要作用。与疾病相关的肠道微生物群组成变化,即生态失调,已与动脉粥样硬化、高血压、心力衰竭、慢性肾病、肥胖和2型糖尿病等病理状况相关联。除了肠道微生物群组成的改变外,肠道微生物群的代谢潜能也被确定为疾病发展的一个促成因素。最近的研究表明,肠道微生物群可对宿主产生多种影响。事实上,肠道微生物组的功能类似于一个内分泌器官,产生可影响宿主生理的生物活性代谢产物。微生物群通过多种途径与宿主相互作用,包括三甲胺/氧化三甲胺途径、短链脂肪酸途径以及初级和次级胆汁酸途径。除了这些依赖代谢的途径外,不依赖代谢的过程也被认为可能对心血管疾病的发病机制有贡献。例如,与心力衰竭相关的内脏循环充血、肠壁水肿和肠屏障功能受损被认为会导致细菌易位,即细菌产物在体循环中的存在以及炎症状态的加剧。这些被认为也有助于心力衰竭和动脉粥样硬化的进一步发展。本综述的目的是强调微生物群及其代谢产物与心血管疾病的发生和发展之间的复杂相互作用。我们还将讨论肠道微生物群在正常生理中的作用以及调节肠道微生物群落作为新型治疗靶点的潜力。