Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, 220, Cheng-Lin Street, Tianjin, 300162, China.
Heart Center, Beijing Chao Yang Hospital, Capital Medical University, Beijing, 100020, China.
Microbiome. 2018 Apr 3;6(1):66. doi: 10.1186/s40168-018-0441-4.
Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge.
Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and D-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated.
Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.
心肌梗死后心血管重构和心力衰竭是过去几十年导致心肌梗死（MI）相关死亡的主要原因。实验观察表明，肠道微生物群与小鼠易患 MI 有关；然而，在人类中，确定肠道细菌向全身循环的易位是否导致 MI 后心血管事件仍然是一个主要挑战。
在这里，我们对 49 名健康对照个体、50 名稳定型冠心病（CHD）患者和 100 名 ST 段抬高型心肌梗死（STEMI）患者的系统细菌进行了宏基因组分析。我们首次报道 STEMI 患者全身微生物组中微生物丰富度和多样性更高。超过 12%的 post-STEMI 血液细菌由肠道微生物群（乳杆菌、拟杆菌和链球菌）主导。明显增加的肠细菌易位产物（LPS 和 D-乳酸）与全身炎症相关，并预测不良心血管事件。在实验性 MI 后，左心室（LV）功能受损和肠道低灌注通过紧密连接蛋白抑制和肠道黏膜损伤导致肠道通透性升高。通过抗生素治疗阻断肠细菌易位后，MI 小鼠的全身炎症和心肌细胞损伤均得到缓解。
我们的研究结果首次提供了证据，表明 MI 后心血管结局是由肠道微生物群向全身循环的易位驱动的。针对保护肠道屏障和消除肠道细菌易位的新治疗策略可能会减少甚至预防 MI 后的心血管事件。
