Microbial Short Chain Fatty Acids and Blood Pressure Regulation

微生物短链脂肪酸与血压调节

基本信息

批准号：
9899288
负责人：
Jennifer L Pluznick
金额：
$ 40.5万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9899288
关键词：
Affect Antibiotics Antihypertensive Agents Bacteria Binding Blood Blood Circulation Blood Pressure Blood Vessels Chemicals Colon Communication Data Diet Endothelial Cells Endothelium FFAR3 gene Future G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Generations Goals Hypotension Immune Immune response Intestines Kidney Lead Literature Mediating Mediator of activation protein Metabolic Metabolism Microbe Modernization Mus Oral Pathway interactions Peripheral Physiological Physiological Processes Physiology Plasma Play Process Production Reporting Role Signal Pathway Signal Transduction Techniques Testing Vasodilation Volatile Fatty Acids Wild Type Mouse Work absorption blood pressure reduction blood pressure regulation feeding gut bacteria gut microbes gut microbiota in vivo microbial microbiota normotensive novel olfactory receptor public health relevance receptor response sensor small molecule

项目摘要

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.

描述（由适用提供）：最近的研究表明，肠道微生物产生的短链脂肪酸（SCFA）代谢产物与宿主中的G蛋白偶联受体相互作用，以影响宿主生理。我们最近发现，脉管系统中的两个SCFA受体 - GPR41和OLFR78-在血压调节中起着作用。这两个受体对SCFA的血浆水平的变化调节血压。 SCFA是在肠道中作为肠道微生物代谢的副产品产生的，然后被吸收到血液中，以前已显示在调节宿主中的各种物理过程中起着重要作用，包括代谢和免疫增生。我们最近的数据表明，肠道微生物代谢物在血压控制中通过外周血管中的SCFA受体控制了新作用。在这里，我们试图通过检查这种反应后的体内和体内的机制，并通过确定我们是否可以故意操纵肠道微生物SCFA产生以降低正常性或高血压小鼠的血压来更好地理解这一途径。提出的工作调用了各种离体和体内技术，以提高我们对血压调节的理解。这些研究有可能导致潜在的未来临床意义，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。