Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients

BackgroundFibres remain undigested until they reach the colon, where some are fermented by gut microbiota, producing metabolites called short-chain fatty acids (SCFAs). SCFAs lower blood pressure (BP) of experimental models, but their translational potential is unknown. We aimed to determine whether SCFAs lower 24-hour systolic BP (SBP) in untreated participants with essential hypertension. MethodsWe performed a phase II randomized placebo-controlled double-blind cross-over trial using SCFA-supplementation, delivered as acetylated and butyrylated high amylose maize starch (HAMSAB). Twenty treatment-naive hypertensive participants were recruited from the community and randomised to 40g/day of HAMSAB or placebo. Participants completed each arm for three-weeks, with a three-week washout period between them. The primary endpoint was a 24-hour SBP decrease. ResultsParticipants were on average 55.8{+/-}11.2-years old (mean{+/-}SD), had a body mass index (BMI) of 25.7{+/-}2.5km2/m, 30% were female, baseline 24-hour SBP 136{+/-}6mmHg. No adverse effects were reported. After the intervention, the placebo-subtracted reduction in 24-hour SBP was 6.1{+/-}9.9mmHg (P= 0.027). This was independent of age, sex, BMI and study arm. There was no statistical significance in the placebo arm. Day and night SBP were reduced by 6.5{+/-}12.3mmHg (P=0.01) and 5.7{+/-}9.8mmHg (P=0.02), respectively, and 24-h central SBP by 7.2{+/-}14.7 mmHg (P=0.005). HAMSAB increased levels of acetate and butyrate by 7.8-fold (P=0.016), shifted the microbial ecosystem, and expanded the prevalence of SCFA-producers. ConclusionsWe observed a clinically relevant reduction in 24-hour SBP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP.