Gut Microbiome–Modulating therapeutics and lipid profile in metabolic syndrome: A systematic review and meta-analysis of clinical trials

Objectives To evaluate the effects of gut microbiome–modulating interventions (probiotics, prebiotics, synbiotics, and fecal microbiota transplantation) on lipid profile parameters in adults with metabolic syndrome (MetS). Design and data sources Systematic review and random-effects meta-analysis with univariate meta-regression of controlled clinical trials indexed in PubMed, Web of Science, and Scopus through June 2025. Eligibility criteria Controlled clinical trials in adults with MetS diagnosed according to ATP III, IDF, or WHO criteria reporting at least one lipid outcome (total cholestrol (TC), low-density lipoprotein cholestrol (LDL-C), high desntiry lipoprotein cholestrol (HDL-C), or triglycerdies (TG)). Studies without control groups, insufficient data, or populations not meeting full MetS criteria were excluded. Data extraction and synthesis Two reviewers independently screened and extracted data. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analysis (DerSimonian–Laird) generated pooled mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Meta-regression evaluated moderators including age, baseline BMI, intervention dose, duration, and geographic region. Results Nineteen studies comprising 21 trial comparisons and 897 participants were included. Microbiome-modulating interventions were associated with reductions in TC (MD −8.97 mg/dL; 95% CI −12.55 to −5.38) and TG (MD −11.33 mg/dL; 95% CI −19.25 to −3.40), while HDL-C showed no significant change. LDL-C was also reduced in the primary pooled analysis (MD −5.05 mg/dL; 95% CI −9.57 to −0.53); however, this finding should be interpreted cautiously because of substantial between-study heterogeneity (I2 = 73.8%) and loss of statistical significance in sensitivity analyses. Greater lipid reductions were generally observed in trials using higher probiotic doses and longer intervention durations, although moderator effects were not consistent across all lipid outcomes. Conclusions Microbiome-modulating interventions are associated with modest improvements in selected lipid parameters in adults with metabolic syndrome, particularly TC and TG. Evidence for LDL-C reduction is less robust because of substantial heterogeneity and sensitivity to analytical assumptions. Larger, well-standardized clinical trials are required to confirm lipid-specific effects, identify responsive populations, and determine the clinical relevance of these interventions. © 2026 The Author(s).