Gut and Intraplaque Microbiota in Atherosclerosis: Mechanistic Insights and Emerging Therapeutic Targets

Atherosclerosis remains a major cause of cardiovascular morbidity and mortality. Growing evidence suggests that microbiota-host interactions contribute to atherosclerosis through systemic and local mechanisms. This review summarizes current evidence on gut microbiota, microbial metabolites, and plaque-associated microbial signals, and discusses their potential therapeutic implications. Gut dysbiosis may contribute to atherosclerosis through multiple metabolite-dependent, immune, vascular, and metabolic pathways. Recent multi-omics and experimental studies further indicate that microbiota influence vascular biology beyond compositional changes alone. In parallel, plaque-associated microbial signals, potentially originating from the oral cavity or gut, may contribute to local inflammation, oxidative stress, necrotic core expansion, and plaque vulnerability. We further discuss a putative gut-oral-intraplaque axis, a potential local microbial metabolite microenvironment within plaques, and possible cross-kingdom interactions between gut fungi and bacteria. Together, these findings support an integrated framework in which microbiota may shape atherosclerosis through interconnected systemic and local pathways, with potential implications for biomarker development and microbiota-targeted therapies.