Rationale: High-salt diet (HSD) 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 above-mentioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture and fecal microbiota transplantation (FMT). We found that HSD induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, while 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 (AA) 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 (B. fragilis) could inhibit the production of intestinal-derived corticosterone induced by HSD through its metabolite AA. Conclusions: hSIH could be transferred by FMT, indicating the pivotal roles of intestinal flora in hSIH development. HSD reduced the levels of B. fragilis and AA 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.

中文翻译：

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肠道菌群通过调节高盐诱导性高血压中肠源性皮质酮的合成来调节血压。

理由：高盐饮食（HSD）是高血压的最重要危险因素之一。据报道，肠道菌群与高盐诱导的高血压（hSIH）有关。但是，尚未完全阐明肠道菌群在hSIH发病机理中的详细作用。目的：揭示肠道菌群在hSIH发育中的作用和机制。方法和结果：使用16S rRNA基因测序，非靶向代谢组学，选择性细菌培养和粪便菌群移植（FMT）等多种技术研究了上述问题。我们发现HSD在Wistar大鼠中诱发高血压。健康大鼠的粪便菌群可以显着降低高血压大鼠的血压（BP），而hSIH大鼠的粪便菌群具有相反的作用。组成，hSIH大鼠的肠道菌群的代谢和相互关系得到了显着重塑，包括皮质酮水平升高，拟杆菌和花生四烯酸（AA）水平降低，这与BP密切相关。hSIH大鼠的血清皮质酮水平也显着升高。此外，在高血压患者中证实了上述异常。脆弱的拟杆菌（B. fragilis）可以通过其代谢产物AA抑制HSD诱导的肠道衍生的皮质酮的产生。结论：hSIH可以通过FMT转移，表明肠道菌群在hSIH发育中起关键作用。HSD降低了肠道中脆弱的芽孢杆菌和AA的水平，从而增加了肠源性皮质酮的产生以及血清和肠道中皮质酮的水平，从而促进血压升高。这项研究揭示了一种不同于炎症/免疫的新机制，肠道菌群通过这种机制调节血压，即肠道菌群可以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对高血压的影响的理解。