S770 The Effect of Gut Microbiome-Modulating Therapies on Lipid Profile in Metabolic Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression

Introduction: Dyslipidemia, characterized by elevated triglycerides (TG; >150 mg/dL) and reduced high-density lipoprotein (HDL; <50 mg/dL), is a key component of metabolic syndrome (MetS). The human gut microbiome plays a crucial role in physiological homeostasis and is both affected in and by pathological states, including MetS. We aimed to evaluate the impact of gut microbiome-modulating therapies—including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT)—on lipid profile parameters in individuals with MetS. Methods: We performed a systematic review, random-effects meta-analysis and univariate meta-regression of clinical trials indexed in PubMed, Web of Science, and Scopus published through April 2023, to evaluate the influence of gut microbiome therapies on biomarkers of lipidemia (total cholesterol, LDL, HDL, or triglycerides) in adult patients diagnosed with MetS using ATP III, IDF or WHO criteria. Results were depicted as mean differences (MDs) with 95% confidence intervals (CIs), and hetergenity was quantified using I² statistics, whereas univariate linear meta-regressions were conducted using age, body mass index, dosage, intervention duration, and region. Risk of bias was assessed using Cochrane RoB 2 tool. Results: Nineteen studies (21 trial comparisons; n = 897) were included. Gut microbiome interventions significantly reduced total cholesterol (MD: -8.97 mg/dL; 95% CI: -12.55 to -5.38; I² = 43.2%), triglycerides (MD: -11.33 mg/dL; 95% CI: -19.25 to -3.40; I² = 55.9%), and LDL (MD: -5.05 mg/dL; 95% CI: -9.57 to -0.53; I² = 73.8%). HDL levels showed no significant change. Subgroup analyses suggested enhanced effects with higher probiotic doses (≥10¹⁰ CFU/day), ≥12-week interventions, and studies from Europe and the Eastern Mediterranean. Participant age and baseline body mass index significantly moderated lipid outcomes. Conclusion: These findings suggest that microbiome-modulating therapies improve key lipid biomarkers in MetS, supporting their potential as adjunct treatments. The lack of significant impact on HDL highlights the complexity of lipid metabolism modulation through microbiome interventions. Further investigations, including well-designed large-scale clinical trials and meta-regression analyses, are warranted to elucidate the specific mechanisms underlying these effects, determine optimal formulations and target populations, and to further explore sources of heterogeneity.