Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.

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