Abstract P162: Butyrate, a Microbial Metabolite, Attenuates Angiotensin II-induced Hypertension and Gut Dysbiosis

Abstract

Objectives: We have previously established that hypertension (HTN) is associated with gut dysbiosis in rat models and patients with high blood pressure. Gut dysbiosis was associated with an increase in Firmicutes/Bacteriodetes ratio and a decrease in butyrate-producing microbial populations. This led us to hypothesize that infusion of butyrate would overcome gut microbial dysbiosis induced butyrate deficiency and reverse angiotensin II (Ang II)-induced HTN. Design and Method: Four groups of C57BL6 mice were infused with either saline, Ang II (1000ng/kg/min), Ang II + sodium butyrate (1mg/kg), or sodium butyrate alone for 4 weeks. Fecal samples were analyzed by 16S bacterial rDNA sequencing for gut microbiome identification. Intestinal leukocytes were analyzed using FACS. Results: Ang II induced increase in MAP was significantly attenuated in mice co-administrated with butyrate (Control, 102.1±5.7 mmHg; Ang II, 148.3±8.1 mmHg; Ang II+Butyrate, 120.5±11.2 mmHg). Microbiota analysis demonstrated a significant increase of gut dysbiosis in Ang II-HTN that was normalized by butyrate treatment (F/B ratio: Control, 2.6; Ang II, 5.4; Ang II+Butyrate, 2.0). Principal Coordinates Analysis indicated each group in the input phylogenetic tree had significantly different microbial communities. LEfSe analysis showed that there were decreases of beneficial bacteria such as Lactobacillus and Bifidobacterium , and increases of Corynebacterium and Staphylococcus at the genus level of Ang II-HTN mice. Furthermore, inflammatory status of the gut as evidenced by the level of mucosal T cells in lamina propria from these groups showed that there was an increase of CCR2 + Th17 cells in Ang II-HTN mice, but not in butyrate co-treated mice (Control, 15.7%; Ang II, 28.4%; Ang II+Butyrate, 15%). Conclusions: These observations show that gut dysbiosis and the decrease of butyrate producing bacteria are associated with Ang II-HTN. Thus, supplementing butyrate in Ang II treated mice attenuated HTN and reversed gut dysbiosis, as well as normalizing the intestinal Th17. These data suggest butyrate producing bacteria could be considered as a novel probiotic therapy for hypertension.