Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Laboratory of Molecular and Cellular Biology, Montréal Heart Institute, Montréal, QC H1T 1C8, Canada.
Int J Mol Sci. 2021 Jul 28;22(15):8074. doi: 10.3390/ijms22158074.
Hypercholesterolemia plays a causal role in the development of atherosclerosis and is one of the main risk factors for cardiovascular disease (CVD), the leading cause of death worldwide especially in developed countries. Current data show that the role of microbiota extends beyond digestion by being implicated in several metabolic and inflammatory processes linked to several diseases including CVD. Studies have reported associations between bacterial metabolites and hypercholesterolemia. However, such associations remain poorly investigated and characterized. In this review, the mechanisms of microbial derived metabolites such as primary and secondary bile acids (BAs), trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) will be explored in the context of cholesterol metabolism. These metabolites play critical roles in maintaining cardiovascular health and if dysregulated can potentially contribute to CVD. They can be modulated via nutritional and pharmacological interventions such as statins, prebiotics, and probiotics. However, the mechanisms behind these interactions also remain unclear, and mechanistic insights into their impact will be provided. Therefore, the objectives of this paper are to present current knowledge on potential mechanisms whereby microbial metabolites regulate cholesterol homeostasis and to discuss the feasibility of modulating intestinal microbes and metabolites as a novel therapeutic for hypercholesterolemia.
高胆固醇血症在动脉粥样硬化的发展中起着因果作用，是心血管疾病（CVD）的主要危险因素之一，尤其是在发达国家，是全球死亡的主要原因。目前的数据表明，微生物组的作用不仅限于消化，还与几种与包括 CVD 在内的几种疾病相关的代谢和炎症过程有关。研究报告了细菌代谢物与高胆固醇血症之间的关联。然而，这种关联仍未得到充分研究和描述。在这篇综述中，将探讨微生物衍生代谢物（如初级和次级胆汁酸（BAs）、三甲胺 N-氧化物（TMAO）和短链脂肪酸（SCFAs））在胆固醇代谢中的作用机制。这些代谢物在维持心血管健康方面起着关键作用，如果失调可能会导致 CVD。它们可以通过营养和药理学干预来调节，如他汀类药物、益生元和益生菌。然而，这些相互作用背后的机制仍不清楚，将提供对其影响的机制见解。因此，本文的目的是介绍当前关于微生物代谢物调节胆固醇稳态的潜在机制的知识，并讨论调节肠道微生物和代谢物作为治疗高胆固醇血症的新方法的可行性。
