Introduction

Hypertension remains a leading global driver of cardiovascular morbidity and mortality, with rising prevalence and persistently poor rates of blood pressure (BP) control despite existing pharmacological options. Emerging evidence implicates the gut microbiota as a modifiable contributor to BP regulation, with dysbiosis linked to hypertension and probiotic supplementation shown in meta-analyses to reduce systolic BP (SBP) across populations. Most prior work, however, has relied on food-based probiotics or Lactobacillus-dominant formulations, leaving the therapeutic potential of Bifidobacterium species relatively underexplored. In our own cohort of Hong Kong Chinese adults, we identified an inverse relationship between SBP and several Bifidobacterium species (B. adolescentis, B. bifidum, B. longum), plausibly mediated through anti-inflammatory, antioxidative, and GABA-producing mechanisms. Building on this rationale, we propose the potential usage of a Bifidobacterium-based synbiotic formulation, SIM01, as a candidate intervention for lowering blood pressure.

Aims and Methodology

The study is a single-arm, open-label feasibility pilot study enrolling 30 community-dwelling, middle-aged Hong Kong Chinese adults with untreated hypertension. Participants will receive SIM01 for 10 weeks, with study visits at baseline , week 5, and week 10.

The primary objective is to evaluate change in mean seated clinic SBP from baseline to week 10. Secondary objectives include (but are not limited to):

• Changes in clinic and 24-hour ambulatory diastolic and systolic BP
• Shifts in gut microbiome composition and function 
• Mechanistic exploration through plasma short-chain fatty acids (SCFAs) and GABA, and serum inflammatory/oxidative stress markers
• Sex-stratified analysis of BP response, motivated by prior evidence of sex-linked differences in gut microbiome–hypertension associations

Data collection includes clinic and ambulatory BP monitoring, fecal and blood sampling, a 3-day diet diary, and structured adverse event surveillance, with paired t-tests/non-parametric equivalents and linear regression used to assess BP changes and their association with microbiome-derived metabolites.

Expected Outcomes

This study was designed to generate feasibility data and preliminary effect estimates to inform the design and power calculation of a subsequent, larger randomized controlled trial. If SIM01 demonstrates a BP-lowering effect, our findings would support Bifidobacterium-based probiotics as a novel, non-pharmacological adjunct for hypertension management, particularly relevant for individuals unwilling or unable to tolerate conventional antihypertensive therapy, while also clarifying underlying mechanisms involving gut dysbiosis, inflammation, oxidative stress, and microbial metabolite production.