S-57-3: GUT MICROBIAL METABOLITES LOWER 24-HOUR SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS
Authors: Jama Hamdi , RhysJones Dakota , Nakai Michael , Yao Chu K K , Climie Rachel E , Sata Yusuke , Anderson Dovile , Creek Darren J , Head Geoffrey A , Kaye David M , Mackay Charles , Muir Jane , Marques Francine Z 
Published: January 2023

Objective:
Clinical evidence supports that dietary fibre intake lowers blood pressure (BP). Dietary fibres remain intact until they reach the colon. There, they are fermented by gut microbial communities to produce metabolites, particularly short-chain fatty acids (SCFAs). Previous studies, including our own, have demonstrated that supplementation with the SCFAs acetate and butyrate lower BP in experimental models. However, whether dietary supplementation with SCFAs in humans elicits the same reduction in BP is undetermined. We aimed to establish whether a SCFAs-enriched dietary supplement lowers 24-hour BP in participants with essential hypertension.

Design and method:
Twenty untreated hypertensive participants, diagnosed by 24-hour BP using a Mobil-O-Graph device, were recruited for a phase II randomized placebo-controlled double-blind crossover trial. Participants were randomized to receive a daily intervention of 40 g/day of acetylated and butyrylated high amylose maize starch (HAMSAB) or 40 g/day of regular flour or cornflour (placebo). The dietary intervention lasted three weeks, with a three-week washout period following completion. The primary endpoint was a change in 24-hour systolic BP. Secondary endpoints included SCFA levels and changes in gut microbiome.

Results:
Participants were on average 55.8 ± 11.2 (mean ± SD) years of age, had a body mass index (BMI) of 25.7 ± 2.5km2/m, and 30% were female. The baseline 24-hour systolic BP was 136 ± 6mmHg. The dietary intervention was well-tolerated and had high acceptability with 93% compliance. There was no difference in 24-hour systolic BP between the baseline visits (P = 0.55) and the placebo (P = 0.18). After 3-weeks on the HAMSAB diet, the placebo-subtracted treatment 24-hour systolic BP difference was 6.1 ± 9.9mmHg (P = 0.027). These observations were independent of age, sex, BMI and study arm. Day and night systolic BP were reduced by 6.5 ± 12.3mmHg (P = 0.01) and 5.7 ± 9.8mmHg (P = 0.02), respectively, and 24-h central BP by 7.2 ± 14.7 mmHg (P = 0.005). There was no change in stroke volume, cardiac output or heart rate; however, HAMSAB reduced total vascular resistance (P = 0.049). Compared to the placebo, the HAMSAB diet elevated acetic and butyric acid levels by 7.8-fold (P = 0.016). HAMSAB also shifted the gut microbial ecosystem (P = 0.037) and increased the prevalence of the acetate and butyrate producers Parabacteroides distasonis and Ruminococcus gauvreauii (q-value < 0.05).

Conclusions:
We observed a clinically relevant reduction in 24-hour systolic BP 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. Low fibre diets and reduced gut microbial metabolites may be one of the principal reasons for the hypertension epidemic in Western countries.