The Effect Of Berberine On Blood Pressure In Spontaneous Hypertensive Rats By Regulating Gut Microbiota

Objective:To study the mechanisms of berberine regulating gut microbiota and influencing the blood pressure in the spontaneous hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats were used as hypertension negative control rats,and SHR were randomly assigned to four groups as follows:control SHR group without any treatment,berberine treated group,fecal microbiota transplantation(FMT)group,and combined group treated with both berberine and FMT.The total DNA of gut microbiota was used for metagenomic analysis,fecal bacteria and serum samples were used for metabolomics analysis,aortic vessels were stained by Masson,Echocardiography was used to detect structural changes in the heart,serum renin and angiotensin II and were detected by ELISA,and serum biochemical indicators were detected by automatic biochemical analyzer.Results:Berberine,fecal microbiota from WKY and the combination of both Berberine and microbiota from WKY can significantly reduce the blood pressure of SHR.Metagenomics showed that berberine could not only change the composition and function of gut microbiota in SHR,but also increase the abundance of Bacteroides,Eubacterium and Ruminococcus significantly.Meanwhile,Berberine could reduce the abundance of Clostridium,Mycoplasma and Treponema.Microbiota genes related to aspartic and glutamic acid metabolism,alanine metabolism,and pyruvate metabolism were significantly increased,while microbiota genes related to glycolysis/gluconeogenesis,purine metabolism,and aminoacyl-tRNA biosynthesis were decreased.Metabolomics showed that berberine upregulated the signaling pathways,including starch and sucrose metabolism,purine metabolism,and renin secretion in fecal bacteria of SHR,and downregulated signaling pathways,including retrograde endogenous cannabinoid signaling,phenylalanine biosynthesis,and aminoacyl-tRNA biosynthesis.Furthermore,Berberine was also found to upregulate signal pathways,including butyrate metabolism,alanine,aspartic acid,and glutamate metabolism,pyruvate metabolism,and purine metabolism,while downregulate signal pathways,including phenylalanine metabolism,and vitamin digestion and absorption in serum of SHR.Berberine alleviated the intestinal barrier damage,improved aortic vascular fibrosis,and reduced the contents of renin,angiotensin Ⅱ,aldosterone,uric acid,urea nitrogen and xanthine oxidase activity significantly in SHR.Conclusion:Our study showed that both berberine and fecal microbiota from WKY rats could significantly reduce the blood pressure of SHR.The intestinal barrier damage was reduced and the aortic fibrosis was improved after berberine treatment in SHR.Our results also showed that Berberine could regulate RAAS system and purine metabolism by regulating the composition and metabolism of gut microbiota,hence reduce the blood pressure of SHR.Put together,our data provides an important view for further studying the disease development of hypertension.