Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension

Background: Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive. Methods: In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics. Results: The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia–Shigella , Lactobacillus , Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension. Conclusion: In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.