OS 05-10 THE MICROBIAL METABOLITE, BUTYRATE ATTENUATES ANGIOTENSIN II-INDUCED HYPERTENSION AND DYSBIOSIS.

OBJECTIVE: Our previous studies have demonstrated that gut microbial dysbiosis is linked to high blood pressure in patients. This was associated with decreases in butyrate- and acetate- producing microbial populations. Thus, our objective in this study was to investigate the hypothesis that infusion of butyrate would impact dysbiosis, gut immunity and attenuate hypertension.

DESIGN AND METHOD: C57B6 mice were divided into 4 groups; Saline infused, Angiotensin II (750ng/kg/min) infused, Ang II infused and butyrate treated (0.5mg/kg) and butyrate alone treated group. 4 weeks after treatment, fecal samples were analyzed by 16S bacterial ribosomal DNA sequencing for gut microbiome identification. Intestinal leukocytes were harvested by enzyme digestion followed by percoll gradients, and the collected cells were analyzed using FACS.

RESULTS: Ang II caused 46mmHg increase in mean arterial pressure (MAP). Butyrate co-administrated group showed significant reduction in MAP (148.3 ± 8.1 mmHg, Ang II vs. 120.5 ± 11.2 mmHg, Ang II + butyrate). Microbiota analysis demonstrated decreases of bacteroidetes (30.2 ± 4.8%, control vs.14.0 ± 2.6%, Ang II) and gut dysbiosis (F/B ratio 2.66, control vs. 4.38, Ang II) in Ang II infused animals. The genus level analysis showed there were marked decreases of butyrate producing bacteria (3.27 ± 0.8%, control vs. 2.09 ± 0.5%, Ang II) in the Ang II group. Analysis of mucosal T cells in lamina propria from these groups showed that there was a significant increase of CCR2 Th17 cells in Ang II infused mice, but not in butyrate co-treated mice.

CONCLUSIONS: These observations show that gut dysbiosis and the decrease of butyrate producing bacteria are associated with Ang II-induced hypertension. Supplementing butyrate in Ang II treated mice attenuated hypertension and gut dysbiosis, as well as normalizing the intestinal Th17 cells that respond to inflammation. These data suggest that gut bacteria produced butyrate plays an important role in blood pressure regulation and that butyrate producing bacteria could be considered as a novel probiotic therapy for hypertension.