High-fat Diet Promotes Atherosclerosis Through the Microecological-immunological Axis

Cardiovascular and cerebrovascular diseases (CVDs) have become one of the leading causes of death in China. Atherosclerosis (AS) is the common pathological basis, and intestinal flora dysbiosis and its metabolites are deeply involved in the development of AS through the "microecology-immunity axis". High-fat diet leads to imbalance of flora structure, decrease of beneficial bacteria and increase of pathogenic bacteria, damage the intestinal barrier, promote the entry of endotoxins (e.g., LPS) and harmful metabolites (e.g., TMAO, lmP, PAGIn, BCAAs) into the bloodstream, activate immune-inflammation (e.g., NF-KB, NLRP3 pathway), platelet activation and thrombosis, and disrupt the lipid metabolism. Reduction of protective metabolites (e.g., SCFAs) impairs anti-inflammatory and endothelial protective effects. Current intervention studies have shifted from traditional flora regulation to targeting metabolites and signaling pathways (e.g., ADR, FXR, I1R inhibition) and exploring multimodal therapies, such as exercise and traditional Chinese medicine. In the future, this article focus on individualized precision intervention, multi-target synergistic strategy, drug delivery system and reliable biomarker validation to promote the clinical translation of AS prevention and treatment.