Correlation Of Altered Gut Microbiota Composition With The Development Of Hypertension In Renal Transplant Recipients

OBJECTIVE: We analyzed the gut microbiomics and targeted metabolomics of renal transplant recipients to reveal the association between the alteration of gut microbial composition after renal transplantation and the development of hypertension in this group of patients,and to explore the role of gut microbes in the development of hypertension in renal transplant recipients.METHODS: Forty patients who underwent renal transplantation follow-up at the Third Xiangya Hospital of Central South University were recruited and stool samples were collected.30 patients met the inclusion criteria,15 renal transplant recipients who did not develop hypertension served as the KT-CTL,and 15 renal transplant recipients who developed hypertension after transplantation served as the KT-HBp.Data were downloaded from a database with 18 healthy individuals as the CTL group and18 non-renal transplant recipients with hypertension as the HBp group.The V3-V4 region of the 16 S r DNA gene of intestinal microorganisms was sequenced and analyzed using Illumina Mi Seq technology to explore the community structure of gut microbiota.Differential strains were screened by Wilcoxon rank-sum test multivariate statistical analysis and Lef Se analysis.The content of short-chain fatty acids in feces was analyzed using gas chromatography-mass spectrometry,and the correlation between the differential strains and the content of short-chain fatty acids in feces was analyzed by Spearman correlation analysis.RESULTS: Significant differences in gut microbiota composition in healthy individuals compared to renal transplant recipients;significant differences in gut microbiota composition in non-renal transplant recipients with hypertension compared to post-transplant hypertensive patients;Alpha diversity and Beta diversity were significantly different between the KT-HBp and KT-CTL,and further analysis of gut microbial community composition by Wilcoxon rank-sum test analysis and Lef Se analysis revealed that Eshcerichia,Faecalibaculum,Faecalitalea,Ruminococcaceae and Lactobacillales were significantly different.KEGG pathway analysis revealed abnormalities in gut microbiota function of the metabolic pathways to Cellular Processes,Environmental Information Processing and Metabolism in hypertensive patients.GC-MS results showed that acetic acid,propionic acid,and butyric acid were significantly higher in the feces of the hypertensive group than in the control group,and the differential intestinal microorganisms Faecalitalea and Pseudoflavonifractor were negatively correlated with acetate,Faecalibaculum was positively correlated with valerate,and Faecalibaculum and Butyricicoccus were positively correlated with butyrate,Brevibacterium were negatively correlated with propionate and Butyricoccus were positively correlated with propionate.CONCLUSION: Microbiomic results revealed significant differences in the diversity of the gut microbiota between the post-transplant hypertensive group and the group without hypertension after kidney transplantation,and abnormalities in the structure of the gut microbiota after the development of hypertension in kidney transplant recipients.Targeted metabolomics results showed a significant increase in acetic acid,propionic acid and butyric acid in the feces of the post-transplant hypertensive group,and abnormal fecal levels of short-chain fatty acids in hypertensive patients after renal transplantation.