Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension
Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension
复制标题
在高盐诱发的高血压中，肠道菌群通过调节肠源性皮质酮的合成来调节血压
DOI：
10.1161/circresaha.119.316394
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发表时间：
2020-03-27
影响因子：
20.1
通讯作者：
Zhang, Qunye
中科院分区：
文献类型：
--
作者：
Yan, Xuefang;Jin, Jiajia;Zhang, Qunye
理论基础：高盐饮食是高血压最重要的危险因素之一。据报道，肠道菌群与高盐诱导的高血压(Hsih)有关。目的：揭示肠道菌群在HsiH发病中的作用和机制。方法与结果：采用16S rRNA基因测序、非靶向代谢组学、选择性细菌培养和粪便微生物区系移植等多种技术对上述问题进行了研究。我们发现高盐饮食诱导了Wistar大鼠的高血压。健康大鼠的粪便微生物区系能显著降低高血压大鼠的血压，而高血压大鼠的粪便微生物区系则有相反的作用。HsiH大鼠肠道菌群组成、代谢及相互关系发生明显改变，皮质酮水平升高，类杆菌和花生四烯酸水平下降，与血压密切相关。HsiH大鼠血清皮质酮水平也明显升高。此外，上述异常在高血压患者中也得到证实。肠道脆弱类杆菌可通过其代谢产物花生四烯酸抑制高盐饮食诱导的肠源性皮质酮的产生。结论：肠道菌群可通过粪便微生物区系移植转移HsiH，提示肠道菌群在HsiH的发育中起着关键作用。高盐饮食降低了肠道中脆性B和花生四烯酸的水平，从而增加了肠源性皮质酮的生成量和血清和肠道中的皮质酮水平，从而促进了血压的升高。本研究揭示了肠道菌群调节血压的一种不同于炎症/免疫的新机制，即肠道菌群可通过影响类固醇激素水平来调节血压。这些发现丰富了对肠道菌群功能及其在高血压中作用的认识。
Rationale:High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated.Objective:To reveal the roles and mechanisms of intestinal flora in hSIH development.Methods and Results:The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid.Conclusions:hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.