Metagenomic sequencing revealed the regulative effect of danshen and honghua herb pair on the gut microbiota in rats with myocardial ischemia injury

Abstract In recent years, more and more evidence has shown that the disorder of gut microbiota (GM) is closely correlated with myocardial ischemia (MI). Even though Danshen and Honghua herb pair (DHHP) is widely used in treating cardiovascular disease in China and exhibits obvious clinical efficacy on MI, the anti-MI mechanism of DHHP remains and needs to be explored in depth. Thus, in this study, we investigated whether the amelioration effect and molecular mechanism of DHHP on MI was related to regulating GM through pharmacodynamics evaluation and metagenomic sequencing. Histopathological observation results indicated that DHHP treatment could alleviate the pathological changes of myocardial tissue in the acute myocardial ischemia (AMI) rats induced by isoproterenol (ISO) exhibited some pathological changes, especially structural disorder, irregular distribution, and enlargement of the myocardial space. These pathological changes were all alleviated to some extent by DHHP treatment. Biochemical analysis results suggested that compared with the control group, the serum levels of AST, CTn-I, CK-MB, TNF-α in model group rats were notably decreased, and the CAT and SOD level in serum were markedly increased. These abnormal trends were significantly reversed by DHHP treatment. Furthermore, metagenomic sequencing analysis results indicated DHHP could improve disorders in the composition and function of GM in AMI rats, mainly reflected in increasing diversity and richness, and obviously enhancing the abundance of Bacteroides fluxus, Bacteroides uniformis, Bacteroides stercoris, Roseburia hominis, Schaedlerella arabinosiphila and Roseburia intestinalis, and reducing the abundance of Enterococcus avium and Enterococcus canintestini, which were associated with purine metabolism, tyrosine metabolism, cyanoamino acid metabolism, and glutathione metabolism. In conclusion, DHHP may attenuate ISO-induced MI by regulating the structure, composition, and function of GM, thus contributing to further our understanding of the anti-MI mechanisms of DHHP and provide new therapeutic ideas and diagnostic targets for the clinical studies of MI.