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

Abstract

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-naïve 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.

A microbiome‐targeting fibre‐enriched nutritional formula is well tolerated and improves quality of life and haemoglobin A1c in type 2 diabetes: A double‐blind, randomized, placebo‐controlled trial

“…Butyrate also stimulates glucagon‐like peptide‐1 release from intestinal L‐cells, enhancing insulin secretion, modulating gastric emptying and, via central mechanisms, reducing appetite 46,47 . Recent epidemiological and interventional trials have also suggested RS and butyrate reduce blood pressure via proposed anti‐inflammatory and vagal nerve‐mediated mechanisms 48‐50 . Other differences in the Active and Placebo formulas (e.g.…”

“…46,47 Recent epidemiological and interventional trials have also suggested RS and butyrate reduce blood pressure via proposed anti-inflammatory and vagal nerve-mediated mechanisms. [48][49][50] Other differences in the Active and Placebo formulas (e.g. sweetener, fat content and micronutrient profile) may have also impacted outcomes.…”

Short-Chain Fatty Acid Receptors and Blood Pressure Regulation: Council on Hypertension Mid-Career Award for Research Excellence 2021

“…110 However, the role of these 2 bacteria taxa in human arterial stiffness needs to be determined. Of note, there are no published studies showing that SCFAs can lower blood pressure in humans as an intervention (however, there is a promising preprint in this area 111 ).…”