Highlights
- Gut microbiome alterations are implicated in the development and persistence of hypertension, especially in treatment-resistant cases.
- Dietary interventions, probiotics, and even fecal microbiota transplantation (FMT) may beneficially modulate blood pressure via the gut microbiome.
- Mechanistic pathways include immune modulation, metabolic control, renal effects, and gut-brain signaling.
- Rigorous clinical trials are needed to clarify patient selection, optimal interventions, and long-term safety.
Study Background and Disease Burden
Hypertension remains the leading modifiable risk factor for cardiovascular morbidity and mortality globally. Despite advancements in antihypertensive therapies, 15% to 20% of patients have treatment-resistant hypertension, defined as uncontrolled blood pressure despite the use of three or more antihypertensive agents, including a diuretic. This population is at heightened risk for cardiovascular and renal complications. There is a critical unmet need for novel therapeutic approaches, and recent research highlights the gut microbiome as a potential modifiable factor in blood pressure regulation.
Study Design and Scope of the Advisory
This American Heart Association Science Advisory synthesizes preclinical, translational, and early-phase clinical trial data on the role of the gut microbiome in hypertension. The advisory reviews experimental models (animal and human), epidemiological studies, and emerging interventional strategies including dietary modification, probiotics, antibiotics, and FMT. It also identifies key mechanistic pathways and research gaps, aiming to guide future clinical translation.
Key Findings
1. Evidence Linking the Gut Microbiome to Hypertension
Numerous preclinical studies demonstrate that alterations in gut microbiota composition can influence blood pressure. Animal models have shown that transferring the microbiome from hypertensive to normotensive animals can induce hypertension, and vice versa. These findings suggest a causal relationship.
2. Dietary Interventions: Fasting and Salt Intake
Dietary modifications, especially intermittent fasting, have been shown to lower blood pressure in animal models by shifting the gut microbial profile. In humans, a 5-day fast followed by a modified DASH (Dietary Approaches to Stop Hypertension) diet led to significant reductions in 24-hour systolic blood pressure and altered gut microbiome composition in patients with metabolic syndrome. However, responses vary, with some individuals showing significant blood pressure reduction (responders) and others not (nonresponders). The underlying mechanisms may include reductions in glucose exposure in the gut, leading to decreased production of microbial metabolites associated with hypertension, such as uridine diphosphate glucose.
High salt intake disrupts the gut microbial balance, notably depleting Lactobacillus species, which in turn promotes immune activation, increases prohypertensive hormones such as corticosterone, and reduces beneficial microbial metabolites like β-hydroxybutyrate and conjugated bile acids. Restoring the gut microbial balance in high sodium settings may help lower blood pressure by modulating immune and metabolic pathways.
3. Mechanistic Pathways: Kidney and Brain Involvement
Short-chain fatty acids (SCFAs), primarily produced by microbial fermentation of dietary fiber, have been shown to lower blood pressure and protect against cardiac and renal fibrosis in animal models. Two renal G-protein–coupled receptors activated by SCFAs can influence renin release, a key regulator of blood pressure. Depletion of beneficial SCFA-producing bacteria, such as Faecalibacterium, is observed in patients with chronic kidney disease. Restoration of these bacteria in animal models improved kidney function and reduced fibrosis.
The gut-brain axis is another avenue for microbiome influence on blood pressure. Serotonin, produced in a gut microbiome-dependent manner, signals via the vagus nerve to central cardioregulatory regions. Microglial activation and neuroinflammation in these regions are heightened in hypertension and may be influenced by gut-derived immune signals and microbial metabolites.
4. Epidemiological Evidence
Case–control and population-based studies have found significant differences in gut microbiome diversity and composition between normotensive and hypertensive individuals. Lower abundance of butyrate-producing bacteria (e.g., Roseburia, Faecalibacterium) is consistently associated with higher blood pressure. However, heterogeneity in study design, sequencing methods, and confounder adjustment limits the ability to draw causal inferences. Prospective longitudinal studies are needed.
5. Emerging Therapeutic Strategies
- Dietary Fiber and SCFAs: Increased dietary fiber intake lowers blood pressure and cardiovascular risk, likely via increased SCFA production by gut bacteria. However, impaired intestinal absorption or signaling can blunt these benefits.
- Minocycline: This anti-inflammatory antibiotic reduces neuroinflammation and shifts the gut microbiome in hypertensive rodent models. In a small human trial of patients with resistant hypertension, minocycline led to significant reductions in systolic (−5.3 mm Hg) and diastolic (−3.6 mm Hg) blood pressure, particularly in responders, possibly via reduced microglial activation.
- Probiotics: Meta-analyses of randomized controlled trials suggest modest reductions in systolic blood pressure (mean −2.05 mm Hg) with probiotic supplementation. The benefit varies by bacterial strain, dose, and duration, and optimal regimens remain undetermined.
- Fecal Microbiota Transplantation (FMT): FMT from normotensive donors to hypertensive recipients lowers blood pressure in animal models. Human trials are pending, but this approach may offer a direct means to reset the hypertensive microbiome.
Expert Commentary
Current evidence suggests that the gut microbiome is a promising, modifiable target for blood pressure control, particularly in patients with resistant hypertension. However, clinical translation faces challenges, including inter-individual variability, safety concerns, and long-term efficacy. Mechanistic insights—such as the roles of SCFAs, immune activation, and gut-brain signaling—are driving the design of next-generation therapeutics. As highlighted by the American Heart Association, integration of multi-omics data, standardized methodologies, and longitudinal interventions will be critical. Caution is warranted regarding over-the-counter probiotics, as efficacy is strain-specific and the regulatory landscape is evolving.
Conclusion
The gut microbiome represents a novel frontier in hypertension management. Preliminary clinical evidence suggests that interventions targeting the microbiome—ranging from dietary fiber and probiotics to FMT and novel antibiotics—can beneficially modulate blood pressure, especially in resistant cases. Large-scale, well-controlled clinical trials are urgently needed to clarify patient selection, optimize interventions, and establish long-term safety and efficacy. The integration of microbiome science into hypertension management could pave the way for precision medicine approaches in cardiovascular care.
References
1. Yang T, Maki KA, Marques FZ, Cai J, Joe B, Pepine CJ, Pluznick JL, Meyer KA, Kirabo A, Bennett BJ; American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Lifestyle and Cardiometabolic Health. Hypertension and the Gut Microbiome: A Science Advisory From the American Heart Association. Hypertension. 2025 Jul 17. doi: 10.1161/HYP.0000000000000247.
2. Maifeld A, Bartolomaeus H, Löber U, et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nat Commun. 2021;12(1):1970.
3. Marques FZ, Mackay CR, Kaye DM. Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol. 2018;15(1):20-32.
4. Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017;551(7682):585-589.
5. Pluznick JL. Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors. Kidney Int. 2016;90(6):1191-1198.
6. Marques FZ, Nelson E, Chu PY, et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation. 2017;135(10):964-977.