Heart–gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion

Abstract

Background Recent studies have suggested a key role of intestinal microbiota in pathological progress of multiple organs via immune modulation. However, the interactions between heart and gut microbiota remain to be fully elucidated. The aim of the study is to investigate the role of gut microbiota in post ischemia/reperfusion (I/R) inflammatory microenvironment. Methods and Results Here, we conducted a case-control study to explore the association of gut bacteria translocation products with inflammation biomarkers and I/R injury severity in STEMI patients. Then, we used a mouse model to determine the effects of myocardial I/R injury on gut microbiota dysbiosis and translocation. Blooming of Proteobacteria was identified as hallmark of post-I/R dysbiosis, which was associated with gut bacteria translocation. Abrogation of gut bacteria translocation by antibiotic cocktail alleviated myocardial I/R injury via mitigating excessive inflammation and attenuating myeloid cells mobilization, indicating the bidirectional heart–gut–microbiome–immune axis in myocardial I/R injury. Glucagon-like peptide 2 (GLP-2), an endocrine peptide produced by intestinal L-cells, was used in experimental myocardial I/R model. GLP-2 administration restored gut microbiota disorder and prevented bacteria translocation, eventually attenuated myocardial I/R injury through alleviating systemic inflammation. Conclusion Our work identifies a bidirectional communication along the heart–gut–microbiome–immune axis in myocardial I/R injury and demonstrates gut bacteria translocation as a key regulator in amplifying inflammatory injury. Furthermore, our study sheds new light on the application of GLP-2 as a promising therapy targeting gut bacteria translocation in myocardial I/R injury. Translational Perspective This study demonstrates a unique bidirectional communication along the heart–gut–microbiome–immune axis in myocardial I/R injury. Myocardial I/R injury induced gut microbiota dysbiosis and gut barrier disruption thus leading to bacterial translocation and these changes in turn aggravated I/R injury by augmenting inflammation. Furthermore, our study sheds new light on the application of GLP-2 as a promising therapy targeting gut bacteria translocation in myocardial I/R injury. These findings highlight the gut microbiota targeting therapy as a potential therapeutics strategy to attenuate myocardial I/R injury and are of great translational value.

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