Remodeling of the gut microbiome by Lactobacillus johnsonii alleviates the development of acute myocardial infarction.
Remodeling of the gut microbiome by Lactobacillus johnsonii alleviates the development of acute myocardial infarction.
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DOI：
10.3389/fmicb.2023.1140498
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发表时间：
2023
影响因子：
5.2
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中科院分区：
文献类型：
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肠道微生物群落可被体内环境的变化所干扰或修复，是急性心肌梗死(AMI)的致病因素。肠道益生菌在急性心肌梗死后微生物群重构和营养干预中发挥作用。一株新分离的约翰森乳杆菌EU03菌株已显示出作为益生菌的潜力。在此，我们通过对急性心肌梗死大鼠肠道微生物组重构的研究，探讨了强生乳杆菌对心肌的保护作用及其机制。采用超声心动图、组织学和血清心脏生物标志物对左冠状动脉前降支结扎(LAD)诱导的大鼠急性心肌梗死模型进行评估，以评价强生乳杆菌的有益作用。免疫荧光分析显示肠屏障的变化。应用抗生素给药模型评价肠道共生物在改善急性心肌梗死后心功能中的作用。通过元基因组学和代谢组学分析，进一步探讨了强生乳杆菌致富的潜在机制。强生乳杆菌的28天治疗保护了心功能，延缓了心脏病理，抑制了心肌损伤细胞因子，并改善了肠道屏障的完整性。通过提高L.johnsonii的丰度，对微生物组组成进行了重新编程。抗菌素引起的微生物群失调破坏了强生乳杆菌对急性心肌梗死后心功能的改善。琼氏乳杆菌的增菌通过增加小鼠肠道菌群、乳酸菌的丰度，减少与心脏性状和血清代谢生物标记物16，16-二甲基-PGA2和3-O-葡萄糖醛酸脂相关的龙布氏菌、梭状芽孢杆菌UCG-014的丰度，导致肠道微生物群的重塑。这些发现表明，强生乳杆菌对肠道微生物组的重塑改善了急性心肌梗死后的心功能，并可能促进微生物组靶向的营养干预。
The gut microbial community, which can be disturbed or repaired by changes in the internal environment, contributes to the development of acute myocardial infarction (AMI). Gut probiotics play a role in microbiome remodeling and nutritional intervention post-AMI. A newly isolated Lactobacillus johnsonii strain EU03 has shown potential as a probiotic. Here, we investigated the cardioprotective function and mechanism of L. johnsonii through gut microbiome remodeling in AMI rats. A rat model of left anterior descending coronary artery ligation (LAD)-mediated AMI was assessed with echocardiography, histology, and serum cardiac biomarkers to evaluate the beneficial effects of L. johnsonii. The immunofluorescence analysis was utilized to visualize the intestinal barrier changes. Antibiotic administration model was used for assessing the gut commensals’ function in the improvement of cardiac function post-AMI. The underlying beneficial mechanism through L. johnsonii enrichment was further investigated by metagenomics and metabolomics analysis. A 28-day treatment with L. johnsonii protected cardiac function, delayed cardiac pathology, suppressed myocardial injury cytokines, and improved gut barrier integrity. The microbiome composition was reprogrammed by enhancing the abundance of L. johnsonii. Microbiome dysbiosis by antibiotics abrogated the improvement of cardiac function post-AMI by L. johnsonii. L. johnsonii enrichment caused remodeling of gut microbiome by increasing the abundance of Muribaculaceae, Lactobacillus, and decreasing Romboutsia, Clostridia UCG-014, which were correlated with cardiac traits and serum metabolic biomarkers 16,16-dimethyl-PGA2, and Lithocholate 3-O-glucuronide. These findings reveal that gut microbiome remodeling by L. johnsonii ameliorates the cardiac function post-AMI and might advance microbiome-targeted nutritional intervention.