Mohsenzadeh Amin, Pourasgar Sahar, Mohammadi Amirali, Nazari Mahdis, Nematollahi Soroush, Karimi Yeganeh, Firoozbakhsh Parisa, Mohsenzadeh Hossein, Kamali Kasra, Elahi Reza
Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Biology, Faculty of Science, Rasht Branch, Islamic Azad University, Rasht, Iran.
Life Sci. 2025 Nov 15;381:123981. doi: 10.1016/j.lfs.2025.123981. Epub 2025 Sep 21.
The gut microbiota, a dynamic ecosystem of microorganisms inhabiting the human body, plays a pivotal role in modulating host physiology and immune function, with intense implications for the cardiovascular system. Cardiovascular diseases (CVDs) stand out as the leading cause of mortality worldwide. Gut microbiome dysbiosis is implicated in diverse CVDs, such as hypertension, atherosclerosis, coronary artery disease, heart failure, and myocardial infarction, through mechanisms mediated by microbial-derived metabolites. Key compounds include trimethylamine N-oxide (TMAO) (linked to plaque instability), short-chain fatty acids (SCFAs) (which regulate blood pressure and endothelial function), phenylacetylglutamine (PAGln) (a promoter of thrombotic pathways), and bile acids (influencing lipid metabolism). These metabolites serve as both biomarkers of CVD risk and therapeutic targets. Emerging strategies to modulate the gut microbiota, such as precision probiotics, dietary interventions (e.g., fiber-rich or polyphenol-heavy diets), and pharmacologic inhibitors of microbial enzymes (e.g., TMA lyase blockers), highlight the potential for microbiome-directed therapies. However, challenges remain in elucidating causal microbial pathways, standardizing interventions across diverse populations, and translating preclinical findings into clinical practice. In this mechanistic and translational review, we synthesize current evidence on the bidirectional relationship between gut microbial dysbiosis and CVDs. We explore how modifiable factors, including diet, pharmacotherapy, and early-life microbial colonization, reshape gut communities, driving systemic inflammation, metabolic dysfunction, and vascular pathology. Future research must prioritize longitudinal human studies, multi-omics integration, and randomized trials to harness the gut microbiota's full potential in CVD prevention and personalized treatment.
肠道微生物群是栖息在人体中的一个动态微生物生态系统，在调节宿主生理和免疫功能方面发挥着关键作用，对心血管系统有着重要影响。心血管疾病（CVDs）是全球死亡的主要原因。肠道微生物群失调通过微生物衍生代谢物介导的机制与多种心血管疾病有关，如高血压、动脉粥样硬化、冠状动脉疾病、心力衰竭和心肌梗死。关键化合物包括氧化三甲胺（TMAO）（与斑块不稳定性有关）、短链脂肪酸（SCFAs）（调节血压和内皮功能）、苯乙酰谷氨酰胺（PAGln）（血栓形成途径的促进剂）和胆汁酸（影响脂质代谢）。这些代谢物既是心血管疾病风险的生物标志物，也是治疗靶点。调节肠道微生物群的新兴策略，如精准益生菌、饮食干预（如富含纤维或多酚的饮食）和微生物酶的药物抑制剂（如TMA裂解酶阻滞剂），凸显了微生物群导向疗法的潜力。然而，在阐明因果微生物途径、在不同人群中规范干预措施以及将临床前研究结果转化为临床实践方面仍存在挑战。在这篇机制与转化综述中，我们综合了关于肠道微生物失调与心血管疾病之间双向关系的现有证据。我们探讨了包括饮食、药物治疗和早期生命微生物定植在内的可改变因素如何重塑肠道群落，引发全身炎症、代谢功能障碍和血管病变。未来的研究必须优先开展纵向人体研究、多组学整合和随机试验，以充分发挥肠道微生物群在心血管疾病预防和个性化治疗中的潜力。
