Effect of Acute Gut Butyrate Delivery on Blood Pressure in Black Individuals With Hypertension: A Proof-of-Concept Randomized Controlled Study.

BACKGROUND: Hypertension is a global health crisis linked to increased heart disease and stroke. Black individuals have the greatest burden of hypertension and related diseases. Recent research suggests that the gut microbial production of short-chain fatty acids, such as butyrate, is associated with blood pressure (BP) regulation. We hypothesize that acutely increasing gut butyrate would lead to a significant reduction in BP within a 24-hour period. METHODS: Ten Black adults with normal BP and 10 with stage 1 hypertension (age and sex-matched) participated in this study. In a crossover experiment, participants with hypertension randomly self-administered a low dose (5 mmol/L) and a high dose (80 mmol/L) butyrate enema 7 days apart. Blood butyrate levels were measured before and 30 minutes post enema, with BP monitored via 24-hour ambulatory devices. Preintervention fecal samples were sequenced via the V4 region of the 16S rRNA gene and microbiome characteristics assessed. RESULTS: We observed that daytime systolic BP was significantly lower after the 80 mmol/L butyrate enema. There was no significant difference in blood butyrate between controls and the group with hypertension before or after either enema. Microbial diversity did not significantly differ between groups; however, pathways for carbohydrate fermentation were significantly lower with differentially abundance butyrate-producing microbes in participants with hypertension compared with those with normal BP. CONCLUSIONS: This study suggests that increasing gut butyrate availability can improve BP. The findings bolster the evidence that gut butyrate regulates BP and supports studies needed to test strategies to boost gut butyrate availability for BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier NCT04415333.