Hypertension remains a leading global health burden, affecting nearly half of adults in the United States and contributing to more than 124,000 deaths each year. It is a multifactorial condition influenced by both genetics and environmental factors, among which high dietary salt (HDS) intake is one of the most significant. Roughly 50–75% of individuals with hypertension exhibit salt sensitivity, a form of blood pressure (BP) dysregulation characterized by a rise of at least 10 mm Hg in response to excessive sodium consumption. This phenotype represents one of the most common and clinically challenging presentations of hypertension.
While traditional research has focused on renal and vascular dysfunction as key mechanisms behind salt-sensitive hypertension, emerging evidence points to the gut microbiome as a critical player in this process. The intestinal microbiota—a diverse ecosystem of trillions of microorganisms—contributes to numerous aspects of human physiology, including metabolism, immune regulation, and vascular health. Of particular interest are short-chain fatty acids (SCFAs), metabolites produced by gut bacteria during the fermentation of dietary fibers. These molecules, such as acetate, propionate, and butyrate, have systemic effects through G-protein-coupled receptors (Gpr41/FFAR3 and Olfr78/OR51E2), which are highly expressed in vascular and renal tissues and play direct roles in BP regulation.
When gut microbial balance is disrupted—a condition known as dysbiosis—SCFA production declines, potentially contributing to hypertension through altered vascular tone, inflammation, and endothelial dysfunction. Understanding this relationship offers a promising opportunity for microbiome-targeted therapies that could complement or even replace traditional antihypertensive strategies.
Purpose and Methodology
The reviewed study aimed to map current scientific knowledge on the connection between the gut microbiome, SCFAs, and salt-sensitive hypertension, highlighting both human and animal research up to August 2024. Following JBI scoping review methodology, investigators searched PubMed using the terms “microbiome” and “hypertension.” Eligible studies included those examining gut microbiota or SCFA influence on salt-sensitive BP regulation in either human or animal models. Non-English publications, reviews, and unrelated studies were excluded.
Two independent reviewers screened articles by title and abstract, with full-text assessments resolving disagreements through consensus. For human trials, data collection focused on study design, participant population, type of intervention, and observed effects on BP, microbiome composition, and SCFA levels. Animal studies were similarly analyzed, with interventions categorized as dietary, prebiotic, probiotic, postbiotic, or live biotherapeutic treatments.
Results and Key Findings
The search process initially identified 2,071 studies, with an additional 255 obtained through reference tracking. After removing duplicates, 1,300 studies remained for screening. Ultimately, 24 studies met the inclusion criteria—9 human and 15 animal trials.
Most human studies were observational (n = 6), comparing gut microbiome differences between hypertensive and normotensive participants. These studies consistently revealed reduced microbial diversity and lower SCFA levels in hypertensive individuals. The remaining three human trials were interventional, exploring whether modifying diet or microbiota could improve BP outcomes. Two studies implemented sodium-restricted diets, while one used prebiotic supplementation to enhance SCFA production. Each reported favorable effects on BP reduction and microbial composition.
Animal models—mostly rats and mice—provided more mechanistic insights. All 15 studies were interventional, examining how microbiome manipulation influenced BP. The interventions included:
- Dietary changes (n = 9), such as high-fiber or low-salt diets, which restored SCFA production and normalized BP.
- Probiotic therapies (n = 1), demonstrating improved gut balance and reduced vascular resistance.
- Postbiotic treatments (n = 4), using bacterial metabolites directly to lower BP.
- Live biotherapeutic products (n = 4), where live bacterial strains acted as biological agents to modulate host metabolism and inflammation.
Remarkably, all animal interventions produced measurable reductions in blood pressure, underscoring the gut’s influence on cardiovascular regulation. These preclinical findings align with limited but encouraging human data suggesting that restoring microbial balance could mitigate salt-induced BP elevation.
Conclusion
This scoping review emphasizes the growing recognition of the gut–blood pressure axis as a novel therapeutic target for salt-sensitive hypertension. Evidence from both human and animal studies demonstrates that gut microbiota composition and SCFA metabolism profoundly affect vascular and renal pathways involved in BP control.
Despite promising results, significant knowledge gaps persist. Human data remain limited in scale and duration, and standardized methods for evaluating microbiome-based therapies are lacking. Future research should aim to clarify optimal bacterial strains, effective prebiotic or postbiotic formulations, and the long-term safety of live biotherapeutic interventions.
Ultimately, these insights highlight an exciting paradigm shift: rather than focusing solely on sodium intake and pharmacologic therapy, modifying the gut microbiome may represent a powerful new strategy for preventing and managing hypertension in the era of personalized medicine.