Microbial Short Chain Fatty Acids and Blood Pressure Regulation

 描述（由申请人提供）：最近的研究表明，肠道微生物产生的短链脂肪酸（SCFA）代谢物与宿主中的G蛋白偶联受体相互作用，影响宿主生理学。我们最近发现，血管系统中的两种SCFA受体-Gpr 41和Olfr 78-在血压调节中发挥作用。这两种受体响应SCFA血浆水平的变化来调节血压。SCFA作为肠道微生物代谢的副产物在肠道中产生，然后被吸收到血流中，并且先前已显示在调节宿主的各种生理过程中发挥重要作用，包括代谢和免疫反应。我们最近的数据表明，肠道微生物代谢产物通过外周血管系统中的SCFA受体在血压控制中发挥了新的作用。在这里，我们试图更好地了解这一途径，通过检查这种反应的机制离体和体内，并通过确定我们是否可以有目的地操纵肠道微生物SCFA的生产，以降低血压正常或高血压小鼠的血压。拟议的工作调用各种离体和体内技术，以促进我们对血压调节的理解。这些研究有可能导致潜在的令人兴奋的未来临床意义，因为我们的数据表明，肠道微生物代谢的变化有可能改变基线血压。

 DESCRIPTION (provided by applicant): Recent studies have demonstrated that short chain fatty acid (SCFA) metabolites generated by gut microbes interact with G-protein coupled receptors in the host to affect host physiology. We recently found that two SCFA receptors in the vasculature - Gpr41, and Olfr78 - play roles in blood pressure regulation. These two receptors modulate blood pressure in response to changes in plasma levels of SCFAs. SCFAs are produced in the gut as a byproduct of gut microbial metabolism and are then absorbed into the bloodstream, and have previously been shown to play important roles in modulating a variety of physiological processes in the host, including metabolism and immune responses. Our recent data demonstrate a novel role for gut microbial metabolites in blood pressure control via SCFA receptors in the peripheral vasculature. Here, we seek to better understand this pathway by examining the mechanism underlying this response ex vivo and in vivo, and by determining whether we can purposefully manipulate gut microbial SCFA production in order to lower blood pressure in either normotensive or hypertensive mice. The proposed work invokes a variety of ex vivo and in vivo techniques in order to advance our understanding of blood pressure regulation. These studies have the potential to lead to potentially exciting future clinicl implications, as our data suggests that changes in gut microbial metabolism have the potential to modify baseline blood pressure.