Intestinal microbiota after angiotensin receptor blockers therapy exerts a protective effect against hypertensive damages
Background: Dysbiosis of gut microbiota has been reported to be implicated in hypertension, and drug-host-microbiome interactions have draw considerable attention. However, the causal role of angiotensin receptor blockers (ARB)-shaped gut microbiota in its anti-hypertensive effect is not fully understood. In this study, we assessed the influence of ARB-modified gut microbiome on blood pressure (BP), vasculature, and intestine, and evaluated the alterations in intestinal transcriptome and serum metabolome. Methods: Hypertensive patients with well-controlled BP under ARB therapy were used as human donors; SHRs receiving NS or valsartan were applied as animal donors. Histological and immunofluorescence staining were used to assess the aorta and small intestine; 16S rDNA amplicon sequencing was used to asses bacteria after treatment. Transcriptome analysis and metabonomics data processing and analysis were used to assess intestinal transcriptome and serum metabolome, respectively. Results: FMT improved hypertension by ameliorating tissue injuries, reducing collagen deposition and reactive oxygen species (ROS) accumulation in vasculatures and alleviating intestinal structure impairments. Meanwhile, FMT resulted in the reconstruction of gut microbiota in SHR recipients, especially by decreasing the relative abundance of Lactobacillus, Aggregatibacter and Desulfovibrio etc. Moreover, ARB-treated microbes increased intestinal Ciart, Per1, Per2, Per3, and Cipc mRNA levels and decreased Nfil3 and Arntl expression. In addition, circulating metabolites, including 6beta-Hydroxytestosterone and Thromboxane B2, were dramatically reduced by ARB-FMT.  Conclusions: These data suggest that gut microbiota has a pivotal role in the therapeutic effects of ARB upon hypertension, which provides insights into the crosstalk between anti-hypertensive medicines and the gut microbiome.