Microbial Interventions to Control And Reduce Blood Pressure In Australia (Microbia): Rationale And Design of A Double-Blinded Randomised Cross-Over Placebo Controlled Trial

Abstract Background: Hypertension is a prevalent chronic disease worldwide that remains poorly controlled. Recent studies support the concept that the gut microbiota is involved in the development of hypertension, and that dietary fibre intake may act through the gut microbiota to lower blood pressure (BP). Resistant starch is a type of prebiotic fibre which is metabolized by commensal bacteria in the colon to produce short-chain fatty acids (SCFA), including acetate, propionate, and butyrate. Previous work in pre-clinical models provide strong evidence that both prebiotic fibre as well as SCFAs (i.e. postbiotics) can prevent the development of hypertension. The aim of this clinical trial is to determine if acetylated and butyrylated modified resistant starch can decrease BP of hypertensive individuals via the modulation of the gut microbiota and release of high levels of SCFAs. Methods: This is a phase IIa double-blinded, randomised, cross-over, placebo controlled trial. Participants are randomly allocated to receive either a diet containing 40g/day of the modified resistant starch or placebo (corn starch or regular flour) for three weeks on each diet, with a three week washout period between the two diets. BP is measured in the office, at home, and using a 24 hour ambulatory device. Arterial stiffness is measured using carotid-to-femoral pulse wave velocity. Our primary endpoint is a reduction in ambulatory daytime systolic BP. Secondary endpoints include changes to circulating cytokines, immune markers, and modulation to the gut microbiome. Discussion: The findings of this study will provide the first evidence for the use of a combination of pre- and postbiotics to lower BP in humans. The results are expected at the end of 2021.Trial registration: Australia and New Zealand Clinical Trial Registry ACTRN12619000916145, registered on 1/07/2019.