Natural products like polyphenols and berberine modulate gut microbiota to target atherosclerosis pathwaysNatural products may target gut health to impact heart disease

BackgroundAtherosclerosis (AS) is a chronic inflammatory vascular disease characterized by lipid accumulation, endothelial dysfunction, immune dysregulation, and plaque formation. Beyond conventional lipid-related mechanisms, gut microbiota dysbiosis and microbiota-derived metabolites have emerged as important regulators of atherogenesis. Natural products, including polyphenols, flavonoids, alkaloids, fatty acids, polysaccharides, saponins, and terpenoids, may modulate AS by reshaping gut microbial ecology and metabolic outputs.MethodsThis narrative review qualitatively synthesized English-language studies published from 2016 to 2026, with emphasis on recent preclinical and emerging clinical evidence. Literature was retrieved from PubMed and Google Scholar using terms related to natural products, gut microbiota, and atherosclerosis. Evidence was integrated across natural product categories, microbial metabolites, host signaling pathways, preclinical models, clinical observations, and translational limitations.ResultsNatural products consistently acted on convergent microbiota-dependent pathways rather than isolated mechanisms. They reduced trimethylamine/trimethylamine N-oxide production, promoted short-chain fatty acid generation, remodeled bile acid metabolism, and modulated microbial tryptophan-derived metabolites. These metabolic changes were associated with improved intestinal barrier integrity, suppression of TLR4/NF-κB and NLRP3-mediated inflammation, immune rebalancing, reduced oxidative stress, enhanced cholesterol efflux, and attenuation of plaque-related phenotypes. Polyphenols and berberine showed relatively stronger mechanistic support, whereas polysaccharides, saponins, terpenoids, and complex formulas remain mainly exploratory. Most evidence derives from animal and in vitro studies, while clinical studies remain limited by small samples, short follow-up, heterogeneous interventions, surrogate endpoints, and insufficient causal validation.ConclusionsNatural products provide an integrated framework for targeting the gut microbiota–metabolite–vascular pathology axis in AS. Although current evidence supports their biological plausibility and adjunctive therapeutic potential, standardized preparations, causal microbiome validation, multi-omics-based biomarkers, and well-designed clinical trials with vascular or cardiovascular endpoints are required before clinical translation.