Study On Gastrointestinal Microbiota And Its Relationship With Bile Acid Metabolism In Hypertensive Patients With Or Without Nephropathy

Objective: To study the characteristics of gut microbiota and to explore the relationship between the underlying mechanisms of bile acid metabolism and intestinal microbiota changes in patients with and without nephropathy compared with health control.Methods: By a cross-sectional study,16 S r RNA sequencing and analysis was performed on total of 86 individual stool samples from the healthy control group,the hypertensive with no nephropathy group and the hypertensive with nephropathy group,including 19 healthy controls,44 hypertensive patients with no nephropathy,and 23 patients with hypertensive nephropathy.The relationship between the microbiota and bile acid profile was analyzed by CCA/RDA.The R pheatmap package was used to analyze whether the microbiome was significantly correlated with bile acid,and to calculate the Spearman coefficient.The function of microbiome was analyzed by Kyoto Encyclopedia of Genes and Genomes(KEEG),the predictive function was analyzed by ANOVA and Dunnett’s test to see if there were significant differences among the groups.Results:1.overall gut microbial composition compared with hypertensive and healthy controls is no significance calculated by alph diversity and beta diversity.The Firmicutes to Bacteroidetes ratio(F/B ratio)of the hypertension with no nephropathy patients was higher than their health peer(P <0.01),however there was no difference compared with hypertensionrelated kidney disease group.2.The content of Coprococcus eutactus and Ruminococcus torques in the hypertension with no nephropathy group was significantly increased,while the hypertension with nephropathy group had a higher abundance of Veillonella parvula and Oxalobacter formigenes.Compared to the healthy controls,the abundance of Bacteroides ovatus,Clostridium Ramsum,Prevotella copri,Erysipelothrix spp.is significantly reduced.3.DCA was positive correlated with Anaerostipes(R = 0.46,P <0.01),Firmicutes(R = 0.37,P <0.05)and Clostridium(R = 0.38,P <0.05),and was negatively correlated with Escherichia(R =-0.43,P <0.01),Enterobacteriaceae(R = 0.48,P<0.05),and Proteobacteria(R = 0.47,P<0.05).GDCA was negatively correlated with Escherichia(R =-0.41,P<0.05)and was positively correlated with Oscilillospira(R = 0.37,P <0.05),which was positively related to TLCA(R = 0.38,P <0.05)and was negatively related to CDCA(R =-0.37,P <0.05).A negative correlation between Prevotella and TCDCA(R =-0.37,P <0.01),and a positive correlation between Coprococcus and GLCA(R = 0.32,P <0.05)were found.4.Compared with the healthy control,in the hypertension with no nephropathy group,the anabolic metabolism of glycolipids(P=0.034),Dglutamine and D-glutamic acid metabolism(P=0.014)were statistical different.Conclusions:1.Compared with hypertensive and healthy controls,the overall gut microbial composition is no significance.F/B were significantly increased in hypertension patients with or without nephropathy.2.The characteristic microflora of hypertension with no nephropathy are coprococcus eutactus and Ruminococcus torques;the characteristic microflora of hypertension with nephropathy are Veillonella parvula and Oxalobacter formigenes;and characteristic microflora of healthy population are Bacteroides ovatus,Clostridium Ramsum,Prevotella copri,Erysipelothrix spp.3.The level of CDCA in the hypertensive patients with no nephropathy is higher than that it either in the healthy control group or the hypertensive nephropathy group,which may be related to the bile salt hydrolysis of Bacteroides and Clostridia.4.D-glutamine and D-glutamate metabolism,anabolic metabolism of glycolipids may be involved in the occurrence and development of hypertension.