Moderation of gut microbiota and bile acid metabolism by chlorogenic acid improves high-fructose-induced salt-sensitive hypertension in mice

Chlorogenic acid (CGA) is a natural compound with many important pharmacological effects including anti-hypertension. This study aimed to investigate the anti-hypertensive effect of CGA on high-fructose-induced salt-sensitive hypertension and the underlying mechanism. Hypertension was induced in male C57BL/6 mice by 20% fructose in drinking water plus 4% sodium chloride in the diet (HFS) for 8 weeks. CGA (50, 100 or 200 mg kg^-1 d^-1) was orally administered to HFS-treated mice. The blood pressure of mice was recorded via the tail cuff method. The structure of gut microbiota and profiles of bile acids (BAs) in the serum were determined. Here, we found that HFS-elevated systolic blood pressure was greatly attenuated by CGA. The microbiota analysis showed that CGA restructured the HFS-treated gut microbiota, and markedly enriched Klebsiella. Oral administration of a Klebsiella isolate, Klebsiella oxytoca, also exhibited an anti-hypertensive effect in HFS-fed mice. Furthermore, we found that CGA and CGA-enriched K. oxytoca enhanced the expression of colonic Farnesoid X Receptor (FXR), modulated BA metabolism and enriched some BAs including deoxycholic acid (DCA) in the serum of HFS-fed mice. Treatment with DCA improved phenylephrine-induced vasoconstriction in arterioles of mice and attenuated hypertension in HFS-fed mice, suggesting that DCA serves as a link between gut microbiota and blood pressure. Our results clearly demonstrate that CGA attenuates HFS-induced hypertension in mice by modulating gut microbiota and BA metabolism. These findings provide insights into the potential mechanism of CGA for the treatment of hypertension.