Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Center for Clinical Genomics, Cleveland Clinic, Cleveland, OH, USA.
Curr Atheroscler Rep. 2017 Aug 25;19(10):39. doi: 10.1007/s11883-017-0675-9.
Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis.
We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.
自人类微生物组计划编制以来，近年来，对微生物群介导的健康风险的研究受到了关注。我们不再认为我们的肠道微生物群是一组无生命的微生物，它们在体内存在而没有后果。在这篇综述中，我们讨论了最近的发现，这些发现进一步加深了我们对肠道微生物群与动脉粥样硬化之间关系的理解。
我们评估了阐明感染、免疫、代谢改变以及细菌产物（如免疫激活剂或饮食代谢物）与动脉粥样硬化发展之间关系的现有研究。特别是，我们批判性地检查了最近关于新型依赖于微生物群的饮食代谢产物三甲胺 N-氧化物（TMAO）的临床和机制发现，TMAO 已被牵连到动脉粥样硬化中。这些发现现在正在与微生物组谱分析的进展相结合，这增强了我们询问肠道微生物组功能作用并开发靶向治疗策略的能力。肠道微生物群是一个多方面的系统，它正在揭示动脉粥样硬化发展和进展的新贡献者。在这篇综述中，我们讨论了历史和新的贡献者，同时突出了 TMAO 故事，主要是作为超越解析微生物组成以阐明促进（或预防）动脉粥样形成的下游机制的各种途径的一个例子，希望将这些发现从实验室转化为临床。
