Genetic, Epigenetic and Dietary Salt effects on Microbiota and Hypertension

7.项目总结/摘要 遗传学、表观遗传学和环境因素，饮食中的盐是最大的因素， 盐敏感性高血压的发展是众所周知的，并进行了深入的研究。加上这些因素，新 来自我们实验室和其他实验室的证据表明，肠道微生物群构成了一个重要的附加因素， 影响个体血压的程度。宿主基因组是“刚性的”，而微生物组 相对灵活（因为它相对更容易改变肠道微生物群的组成）使其成为一种 有吸引力的主张，考虑微生物群驱动的高血压临床管理策略。 然而，关于基因组、表观基因组或膳食盐如何改变微生物群的基本问题仍然有待解决。 测定为了解决这一问题，目前的提案利用了 对最流行的盐敏感性高血压大鼠模型Dahl Salt的基因组和表观基因组的研究， 敏感（S）大鼠，并建议研究宿主遗传和表观遗传因素如何与肠道和 口腔微生物群，以促进盐敏感性BP调节。据我们所知，这将是第一个有条理的 盐敏感性高血压中宿主基因组-微生物组相互作用的研究。我们的工作并 预计将提供重要的基本见解，但未发现的新机制， 微生物群作为一个新的参与者参与高血压的发生。

7. Project Summary/Abstract Genetics, epigenetics and environmental factors, dietary salt being the largest one, contributing to the development of salt-sensitive hypertension is well known and intensely researched. Added to these factors, new evidence from our laboratory and others indicates that gut microbiota constitute an important additional factor influencing the extent of blood pressure of an individual. The host genome being `rigid', whereas the microbiome being relatively flexible (because it is relatively easier to alter compositions of gut microbiota) makes it an attractive proposition to contemplate microbiota-driven strategies for the clinical management of hypertension. However, fundamental questions on how the genome, epigenome or dietary salt modify microbiota remain to be determined. To address this point, the current proposal takes advantage of preliminary data generated with studies on the genome and epigenome of the most popular salt-sensitive hypertensive rat model, the Dahl Salt- sensitive (S) rat and, proposes to study how the host genetic and epigenetic factors interact with both gut and oral microbiota to facilitate salt-sensitive BP regulation. To our knowledge, this will be the first methodical investigation into the host genome-microbiome interactions in salt-sensitive hypertension. Our work will be expected to provide fundamental insights into important, yet undiscovered new mechanisms governing the genesis of hypertension involving the microbiota as a new player.