Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study

Abstract

Background Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed. Methods A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety. Discussion Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling. Trial registration ClinicalTrials.govNCT04406129. Registered on May 28, 2020

How Dietary Fibre, Acting via the Gut Microbiome, Lowers Blood Pressure

“…Other potential approach includes FMTs from healthy donors with enriched SCFA-producing bacteria or T regs -inducing bacteria. An RCT on the potential of FMTs to lower BP has been described [ 84 ], but the results are yet to be available. Moreover, interkingdom interactions within the gut could be leveraged: bacteriophages could be used to target and kill specific bacteria that produce detrimental metabolites from a low-fibre diet.…”

Effect of focused power ultrasound-mediated perirenal fat modification on primary hypertension: protocol of a multicenter, randomized, double-blinded, sham-controlled study

“…Based on the outcome of the pilot study, the mean change in office SBP from baseline to 1 month was expected to 10 mmHg with a deviation of 13 mmHg in the PFM group. Meanwhile, we assumed that a mean difference of office SBP was 5 mmHg [ 15 , 16 ] with a deviation of 13 mmHg in the sham control group. The sample size was calculated as 100 in each group with a power of 80%, a two-sided significance level of 5%, and a drop-out rate of 15%.…”

Prospects for Leveraging the Microbiota as Medicine for Hypertension

“…Revealing the potential of this approach, transplantation of healthy donor gut microbiota lowered BP in patients with hypertension, and there are ongoing trials dedicated to determining the efficacy and safety of fecal microbiota transplantation and gut microbiota restoration in hypertension. 136,137…”

“…Revealing the potential of this approach, transplantation of healthy donor gut microbiota lowered BP in patients with hypertension, and there are ongoing trials dedicated to determining the efficacy and safety of fecal microbiota transplantation and gut microbiota restoration in hypertension. 136,137 Another novel avenue for modulating the gut microbiota in hypertension is via manipulation of the bacteria itself, where genetic engineering of protective bacteria like Lactobacillus spp. to overexpress human angiotensinconverting enzyme 2 demonstrated BP-lowering effects in a sex-specific manner.…”