Abstract
BACKGROUND: Cardiovascular diseases, driven significantly by dyslipidemia, remain a leading global mortality risk. Emerging evidence indicates that Lactobacillus plantarum (L. plantarum), which is a probiotic commonly used in a variety of food products, may contribute to the regulation of blood lipids, although prior studies report inconsistent efficacy and lack mechanistic clarity. This study aimed to evaluate the effects of L. plantarum supplementation on blood lipid profiles and explore its potential mechanisms through a systematic review, meta-analysis, and network pharmacology. METHODS: We performed a comprehensive literature search across PubMed, Cochrane Library, EMBASE, and other databases. Meta-analysis was performed using random-effects models to assess changes in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Network pharmacology was employed to predict molecular targets and pathways. RESULTS: Twenty-six randomized controlled trials (RCTS) involving 2104 participants were included. L. plantarum supplementation significantly reduced TC (SMD: -0.233; 95% CI: -0.458, -0.008; p = 0.042), TG (SMD: -0.227; 95% CI: -0.432, -0.021; p = 0.030), and LDL-C (SMD: -0.251; 95% CI: -0.477, -0.025; p = 0.029), but not HDL-C. Subgroup analyses revealed greater efficacy with interventions lasting >8 weeks and single-strain formulations. Network pharmacology analysis highlighted IL-17/TNF signaling pathway, bile secretion, and other pathways as key mechanisms and targets such as PPARG and MMP9 as key targets. CONCLUSIONS: L. plantarum demonstrates significant lipid-lowering effects, particularly for TC, TG, and LDL-C, with sustained use and single-strain formulations yielding optimal outcomes. Mechanistically, it may modulate inflammation, oxidative stress, and lipid metabolism. These findings can support the development of a functional food and dietary supplement using L. plantarum to assist in the treatment of hyperlipidemia, though heterogeneity and strain-specific effects warrant further investigation.