Microbiota-mediated mechanisms of natural products in atherosclerosis: focus on metabolic and inflammatory pathways
Abstract
BACKGROUND: Atherosclerosis (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.
METHODS: This 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.
RESULTS: Natural 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…
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