European Journal of Cardiovascular Medicine

Metabolic Syndrome (MetS) is a multifaceted clinical condition characterized by a cluster of metabolic abnormalities, including central obesity, dyslipidemia, hypertension, and insulin resistance, which together contribute to an increased risk of developing cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) (1). The global prevalence of MetS is escalating, making it a significant public health concern. Studies have indicated that chronic low-grade inflammation plays a critical role in the pathogenesis of MetS and its associated complications (2).

The gut microbiota, a complex community of trillions of microorganisms residing in the human gastrointestinal tract, has been increasingly recognized as a key player in metabolic health. It influences energy metabolism, glucose homeostasis, lipid metabolism, and immune regulation (3). Disruption of gut microbiota composition, termed dysbiosis, has been linked to various metabolic disorders, including obesity, insulin resistance, and MetS (4).

Recent evidence suggests that gut microbiota modulation through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation may help in reducing systemic inflammation and improving metabolic profiles in individuals with MetS (5,6). Probiotic supplementation, in particular, has demonstrated promising results in reducing inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) (7).

Additionally, dietary interventions rich in fibers and polyphenols have been associated with favorable changes in gut microbiota composition, resulting in improved lipid metabolism and insulin sensitivity (8). Despite these findings, the exact mechanisms by which gut microbiota influences inflammation and cardiovascular risk in MetS remain incompletely understood, necessitating further investigation.

This study aims to evaluate the impact of gut microbiota modulation through dietary interventions and probiotic supplementation on inflammatory markers and cardiovascular risk in patients with MetS. Understanding these relationships may contribute to developing novel therapeutic strategies for managing MetS and reducing its cardiovascular complications.

Study Design and Participants:

This randomized controlled trial was conducted over a 12-week period involving 120 adult patients aged between 30 and 65 years diagnosed with Metabolic Syndrome (MetS) based on the International Diabetes Federation (IDF) criteria. The participants were recruited from outpatient clinics and were randomly assigned to three groups:

• Group A (Dietary Intervention): Received a high-fiber, polyphenol-rich diet aimed at enhancing gut microbiota composition.
• Group B (Probiotic Supplementation): Received daily oral probiotic capsules containing Lactobacillus and Bifidobacterium species.
• Group C (Control Group): Received standard care and dietary advice without any specific intervention.

Inclusion and Exclusion Criteria:

Inclusion Criteria:

• Adults aged 30–65 years.
• Diagnosed with MetS based on IDF criteria.
• Willingness to comply with the intervention protocols.

Exclusion Criteria:

• History of major cardiovascular events.
• Use of antibiotics, prebiotics, or probiotics within the past month.
• Severe gastrointestinal disorders or autoimmune diseases.
• Pregnancy or lactation.

Intervention Protocols:

Participants in Group A followed a structured diet plan rich in dietary fibers, polyphenols, and prebiotics, focusing on whole grains, fruits, vegetables, and nuts. Group B received a daily oral probiotic supplement containing a combination of Lactobacillus acidophilus (5 billion CFU) and Bifidobacterium bifidum (5 billion CFU). Group C received general dietary advice but no specific intervention targeting gut microbiota.

Assessment of Inflammatory Markers and Cardiovascular Risk:

Blood samples were collected from all participants at baseline and after 12 weeks of intervention. Serum inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA) kits.

Cardiovascular risk was assessed by analyzing lipid profiles, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Arterial stiffness was measured using pulse wave velocity (PWV) as an additional indicator of cardiovascular risk.

Statistical Analysis:

Data were analyzed using SPSS software (version 26.0). Continuous variables were presented as mean ± standard deviation (SD). Comparisons between groups were conducted using one-way analysis of variance (ANOVA), followed by post-hoc tests for inter-group comparisons. Paired t-tests were applied for within-group comparisons before and after the intervention. A p-value of less than 0.05 was considered statistically significant.

A total of 120 participants were enrolled in the study and randomly divided into three groups: Group A (Dietary Intervention, n=40), Group B (Probiotic Supplementation, n=40), and Group C (Control Group, n=40). All participants completed the study, with no dropouts reported.

Inflammatory Markers

The mean values of inflammatory markers (CRP, IL-6, and TNF-α) before and after the intervention in all groups are presented in Table 1.

Table 1: Comparison of Inflammatory Markers Before and After Intervention

*Significant reduction compared to baseline (p < 0.05).

The results in Table 1 indicate that both Group A and Group B showed significant reductions in CRP, IL-6, and TNF-α levels after 12 weeks of intervention (p < 0.05). However, no significant changes were observed in the Control Group.

Cardiovascular Risk Indicators

Lipid profiles and arterial stiffness measured by pulse wave velocity (PWV) before and after the intervention are summarized in Table 2.

Table 2: Comparison of Lipid Profiles and PWV Before and After Intervention

*Significant improvement compared to baseline (p < 0.05).

As shown in Table 2, Group A and Group B demonstrated significant improvements in lipid profiles, including reductions in total cholesterol, triglycerides, LDL-C, and increases in HDL-C levels (p < 0.05). Additionally, arterial stiffness as measured by PWV decreased significantly in these groups (p < 0.05). The Control Group did not exhibit any significant changes.

The present study evaluated the impact of gut microbiota modulation through dietary interventions and probiotic supplementation on inflammatory markers and cardiovascular risk in patients with Metabolic Syndrome (MetS). The findings suggest that both interventions significantly reduced inflammatory markers and improved cardiovascular risk profiles compared to standard care.

The observed reduction in inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in Groups A and B is consistent with previous studies demonstrating the anti-inflammatory effects of gut microbiota modulation (1,2). CRP is a well-established marker of systemic inflammation associated with cardiovascular risk (3). Inflammatory cytokines such as IL-6 and TNF-α are known to play critical roles in promoting insulin resistance and endothelial dysfunction, thereby increasing cardiovascular risk (4).

The significant improvement in lipid profiles, particularly the reduction in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), along with increased high-density lipoprotein cholesterol (HDL-C), suggests a positive modulation of lipid metabolism by the interventions (5). Studies have shown that certain dietary components, such as fibers and polyphenols, promote beneficial gut microbial populations capable of improving lipid metabolism (6,7). Probiotics, particularly Lactobacillus and Bifidobacterium species, have been reported to enhance lipid metabolism and reduce hypercholesterolemia through various mechanisms, including bile salt deconjugation and short-chain fatty acid (SCFA) production (8,9).

Furthermore, the reduction in arterial stiffness, as measured by pulse wave velocity (PWV), aligns with findings from previous research indicating that improved gut health can have favorable effects on vascular function (10). Increased SCFA production from dietary interventions has been linked to enhanced endothelial function and reduced arterial stiffness (11).

Dietary interventions rich in prebiotic fibers and polyphenols are known to enhance microbial diversity and stimulate the growth of beneficial bacteria, which contribute to improved metabolic health (12). Similarly, probiotic supplementation has been shown to reduce markers of systemic inflammation, regulate lipid metabolism, and improve gut barrier integrity (13,14).

The findings of this study support previous reports suggesting that gut microbiota modulation could be a promising approach for managing MetS and reducing cardiovascular risk. However, the exact mechanisms by which gut microbiota exerts these effects remain partially understood. Potential mechanisms include modulation of the gut-brain axis, improved gut barrier function, and alterations in bile acid metabolism (15).

Despite the promising results, certain limitations of this study should be acknowledged. The relatively short duration of intervention (12 weeks) may not fully capture the long-term effects of dietary and probiotic interventions on MetS. Additionally, the study did not investigate the specific changes in gut microbiota composition, which would have provided further insight into the mechanisms of action.

Future studies should focus on longer intervention periods, broader patient populations, and the use of advanced techniques such as metagenomic sequencing to elucidate the precise role of gut microbiota modulation in metabolic health. Furthermore, exploring the synergistic effects of combined dietary and probiotic interventions could provide a more comprehensive understanding of their therapeutic potential.

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