Abstract
BACKGROUND: Globally, cardiovascular diseases account for the highest proportion of deaths, highlighting the need for changes in diet and lifestyle, along with safe and effective prophylactic strategies. Among various interventions, probiotics, prebiotics, or their combination as synbiotics have gained preference owing to their multifactorial modulatory potential in attenuating cardiovascular risks. Hence, it was pertinent to explore the comparative prophylactic influence of a synbiotic (Lactiplantibacillus plantarum M10 + Isomaltose) and the cholesterol-lowering drug simvastatin in an experimental atherosclerotic murine model. RESULTS: Eighteen weeks of synbiotic supplementation to Sprague Dawley rats fed with high-cholesterol diet significantly attenuated anthropometric variables such as body weight, BMI, Lee’s Index, organ weight, blood glucose, and lipid profile. Synbiotic treatment also improved oral glucose tolerance, enhanced fecal lipid excretion, and modulated gut microbial composition by increasing beneficial genera (e.g., Ruminococcus, Lactobacillus, Faecalibacterium) and restoring the Bacteroidetes-to-Firmicutes ratio, followed by improvement in groups receiving L. plantarum M10 + HCD and Simvastatin + HCD. Furthermore, synbiotic supplementation enhanced antioxidant levels (SOD and GSH), decreased oxidants (MDA), downregulated NF-κβ expression, pro-inflammatory cytokines (IL-6, TNF-α), reduced MCP-1 and ICAM-1, and elevated IL-10 levels, thereby reducing hepatic steatosis and aortic thickening. CONCLUSIONS: These findings positioned synbiotics not just as a dietary supplements, but also a proactive protectors against diet-induced atherosclerosis, offering a promising prophylactic intervention and needs to be validated clinically. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-026-04840-z.