Co-housing-Mediated Gut Microbiota Transfer Improves Survival in a Mouse Model of Acute Myocardial Infarction

Background: Gut microbiota transfer has been reported to inhibit the progression of atherosclerosis. However, whether gut microbiota transfer suppresses the development of acute myocardial infarction (AMI) remains unknown. Mice are coprophagic, and the therapeutic effect of gut microbiota transfer can be studied by co-housing wild-type (WT) mice with disease model mice. In this study, we investigated the effect of gut microbiota transfer on the development of AMI by co-housing WT mice with our 2/3 nephrectomized triple neuronal/inducible/endothelial nitric oxide synthase (NOS)-knockout mice that exhibit sudden cardiac death due to AMI (AMI mice). Methods and Results: The survival rate was significantly higher in co-housed AMI mice as compared with single-housed AMI mice. Postmortem histopathological analysis indicated that the incidence of myocardial infarction tended to be lower in co-housed AMI mice than in single-housed AMI mice (73% vs. 85%). The abundances of gut bacteria, specifically Bacilli, Lactobacillales, and Lactobacillaceae, were significantly and markedly reduced to almost undetectable levels in single-housed AMI mice compared with single-housed WT mice. In contrast, these populations were considerably preserved in co-housed AMI mice. Fecal concentrations of total short-chain fatty acid and acetic acid were significantly lower in single-housed AMI mice than in single-housed WT mice, whereas those concentrations were substantially maintained in co-housed AMI mice. Notably, long-term oral treatment with 0.35 mM acetic acid in single-housed AMI mice showed a trend toward improved survival, accompanied by significant reductions in systolic blood pressure and fasting blood glucose levels and a slight decrease in plasma total cholesterol levels. CAGE sequencing of heart tissues indicated possible involvements of immunity- and PPAR signalingmediated mechanisms in the beneficial cardiovascular effects of gut microbiota transfer. Conclusions: These results provide the first evidence that co-housing-mediated gut microbiota transfer from WT donor mice improves survival in a mouse model of AMI, potentially involving the restoration of fecal acetic acid levels. Our findings suggest that gut microbiotatargeted interventions may represent a novel therapeutic strategy for the prevention of AMI.