Hypertension is a leading global health concern and a major contributor to cardiovascular diseases (CVD), which account for a significant proportion of morbidity and mortality worldwide (1). Despite the availability of antihypertensive medications, achieving optimal blood pressure control remains a challenge for many patients, necessitating the exploration of alternative and adjunctive therapeutic approaches (2). Recently, gut microbiota has emerged as a key player in the regulation of blood pressure and cardiovascular health, offering a potential target for novel interventions (3,4).

The gut microbiota is a diverse community of microorganisms residing in the gastrointestinal tract, playing a crucial role in various physiological processes, including metabolism, immune regulation, and inflammation (5). Emerging evidence suggests that dysbiosis—an imbalance in the gut microbiota—can contribute to hypertension through multiple mechanisms, such as impaired short-chain fatty acid (SCFA) production, increased systemic inflammation, and altered sympathetic nervous system activity (6,7). Several studies have demonstrated that individuals with hypertension exhibit distinct gut microbiota profiles characterized by reduced beneficial bacteria, such as Lactobacillus and Bifidobacterium, and an increased abundance of pro-inflammatory species (8,9).

Modulating gut microbiota composition through probiotics, prebiotics, and dietary interventions has shown promising effects in lowering blood pressure and improving cardiovascular risk factors (10). Probiotics, which are live microorganisms that confer health benefits, have been found to enhance SCFA production, reduce inflammation, and improve endothelial function (11). Similarly, prebiotics—non-digestible food components that selectively promote the growth of beneficial bacteria—have been associated with improved metabolic and cardiovascular health outcomes (12). Clinical trials have reported significant reductions in systolic and diastolic blood pressure following probiotic and prebiotic supplementation, suggesting a potential therapeutic role in hypertension management (13,14).

Despite these promising findings, the precise mechanisms underlying gut microbiota's influence on blood pressure regulation remain incompletely understood, and further research is required to establish effective gut-targeted interventions for hypertension. This study aims to investigate the impact of gut microbiota modulation on blood pressure and cardiovascular risk factors, contributing to the growing body of evidence supporting microbiota-based strategies for hypertension management.

Study Design and Participants

This randomized controlled trial was conducted to assess the impact of gut microbiota modulation on hypertension and cardiovascular risk factors. A total of 100 hypertensive patients aged 40–60 years were recruited from a tertiary healthcare centre. Participants were randomly allocated into two groups: an intervention group (n=50) receiving a gut microbiota-modulating diet enriched with probiotics and prebiotics, and a control group (n=50) following a standard diet. The study duration was 12 weeks. Informed consent was collected from all participants before enrolment.

Inclusion and Exclusion Criteria

Individuals with diagnosed primary hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) were included. Participants with secondary hypertension, chronic gastrointestinal disorders, antibiotic use in the past three months, or those on immunosuppressive therapy were excluded. Pregnant and lactating women were also not considered for this study.

Intervention and Dietary Plan

The intervention group received a diet rich in probiotics (Lactobacillus and Bifidobacterium species) and prebiotics (inulin, fructooligosaccharides) through fermented dairy products, fiber-rich vegetables, and whole grains. The control group followed their regular diet without additional probiotic or prebiotic supplementation. Participants in both groups were advised to maintain their usual physical activity levels and medication regimens. Dietary adherence was monitored through self-reported food diaries and periodic counseling sessions.

Outcome Measures

Primary outcomes included changes in blood pressure levels, while secondary outcomes included variations in lipid profiles, inflammatory markers, and gut microbiota composition.

• Blood Pressure Measurement: Systolic and diastolic blood pressure were measured using an automated sphygmomanometer at baseline, week 6, and week 12. The average of three readings taken after 5 minutes of rest was recorded.
• Lipid Profile: Fasting blood samples were collected to measure total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides using enzymatic assays.
• Inflammatory Markers: Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were analyzed using enzyme-linked immunosorbent assay (ELISA).
• Gut Microbiota Analysis: Stool samples were collected at baseline and the end of the study. Microbiota composition was analyzed through 16S rRNA sequencing to assess changes in bacterial diversity and relative abundance of key microbial species.

Statistical Analysis

Data were analyzed using SPSS software (version 26.0). Descriptive statistics were used to summarize baseline characteristics. Continuous variables were expressed as mean ± standard deviation (SD) and compared between groups using an independent t-test. A paired t-test was used to assess within-group changes over time. Categorical variables were analyzed using the chi-square test. A p-value of <0.05 was considered statistically significant.

Baseline Characteristics

At the beginning of the study, no significant differences were observed between the intervention and control groups in terms of demographic and clinical characteristics (Table 1). The mean age of participants was 52.3 ± 5.6 years in the intervention group and 51.8 ± 5.3 years in the control group (p=0.72). Similarly, baseline systolic and diastolic blood pressure levels were comparable between the two groups (p=0.78 and p=0.88, respectively). Lipid profiles, including LDL and HDL cholesterol levels, were also statistically similar between the groups (p>0.05).

Table 1: Baseline Characteristics of Participants

Changes in Blood Pressure and Lipid Profile

After 12 weeks of intervention, the intervention group exhibited a significant reduction in systolic blood pressure (−12.5 ± 3.2 mmHg, p=0.002) and diastolic blood pressure (−7.8 ± 2.1 mmHg, p=0.01) compared to the control group, which showed minimal changes (Table 2). LDL cholesterol levels in the intervention group decreased significantly from 128.5 ± 4.6 mg/dL to 113.3 ± 3.9 mg/dL (p=0.004), while HDL cholesterol levels increased from 42.3 ± 2.5 mg/dL to 49.7 ± 3.1 mg/dL (p=0.03).

Table 2: Changes in Blood Pressure and Lipid Profile after 12 Weeks

Inflammatory Markers and Gut Microbiota Composition

A notable reduction in inflammatory markers was observed in the intervention group, with CRP levels decreasing by 22.8% (from 3.5 ± 0.6 mg/L to 2.7 ± 0.4 mg/L, p=0.01), whereas the control group showed a slight, non-significant reduction (p=0.10). Gut microbiota analysis revealed a significant increase in beneficial bacterial species (Lactobacillus and Bifidobacterium) and a decrease in pro-inflammatory species in the intervention group.

These findings suggest that modulation of gut microbiota through dietary interventions and probiotics contributes to improved blood pressure regulation and cardiovascular health. ​​

This study demonstrates that gut microbiota modulation through probiotic- and prebiotic-rich dietary interventions significantly improves blood pressure control and cardiovascular risk factors in hypertensive individuals. Our findings align with previous research indicating a strong association between gut microbiota composition and hypertension (1,2). The observed reductions in systolic and diastolic blood pressure, lipid profile improvements, and decreased inflammation suggest that targeting gut microbiota may be a promising adjunctive strategy for hypertension management.

The role of gut microbiota in regulating blood pressure has gained attention in recent years. Several mechanisms have been proposed, including the production of short-chain fatty acids (SCFAs), regulation of the renin-angiotensin system, modulation of the immune response, and alterations in sympathetic nervous system activity (3,4). SCFAs, such as butyrate and acetate, have been shown to enhance endothelial function and reduce systemic inflammation, contributing to lower blood pressure (5). Our study findings are consistent with previous reports demonstrating that dietary interventions promoting SCFA-producing bacteria lead to significant reductions in blood pressure (6).

Apart from blood pressure regulation, gut microbiota modulation positively influenced lipid metabolism. Participants in the intervention group exhibited a significant reduction in LDL cholesterol and an increase in HDL cholesterol, consistent with previous studies showing that probiotics and prebiotics improve lipid profiles by reducing cholesterol absorption and promoting bile acid metabolism (7,8). Inflammation is a key contributor to hypertension and cardiovascular disease, with elevated CRP and IL-6 levels linked to increased cardiovascular risk (9). The reduction in CRP levels observed in this study supports earlier findings that probiotics exert anti-inflammatory effects by strengthening gut barrier integrity and reducing endotoxin translocation (10,11).

Several clinical trials have evaluated the effects of probiotics on hypertension, with mixed results. A meta-analysis of randomized controlled trials found that probiotic supplementation led to a modest but significant reduction in systolic and diastolic blood pressure (12). Our findings reinforce these observations, highlighting that dietary modulation of gut microbiota can be an effective non-pharmacological approach for managing hypertension. However, differences in study duration, probiotic strains, and dietary interventions may account for variations in outcomes across studies (13).

The observed improvements in cardiovascular health may be attributed to increased abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, which have been reported to reduce blood pressure by modulating the gut-brain axis and lowering systemic inflammation (14). These findings suggest that personalized nutrition strategies targeting gut microbiota composition could complement existing antihypertensive therapies. Future research should focus on identifying specific microbial signatures associated with hypertension and optimizing dietary interventions for individual patients (15).

This study has certain limitations, including a relatively short duration and a moderate sample size. Long-term studies with larger populations are needed to assess the sustainability of blood pressure reductions and cardiovascular benefits. Additionally, gut microbiota composition was analyzed using 16S rRNA sequencing, which provides insights into microbial diversity but lacks functional analysis of microbial metabolites. Future studies incorporating metabolomics and shotgun sequencing may offer a more comprehensive understanding of gut microbiota’s role in hypertension.

Our study provides compelling evidence that gut microbiota modulation through dietary interventions significantly reduces blood pressure, improves lipid profiles, and lowers systemic inflammation in hypertensive patients. These findings support the potential of microbiota-targeted strategies as adjunctive therapies for hypertension management. Further large-scale, long-term studies are warranted to confirm these benefits and explore personalized microbiome-based interventions.

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