Abstract 12596: Manipulation of Gut Microbiota Influences Myocardial Mass in Mice

Abstract

Introduction: Gut microbiota have developed a close relationship with human host during the co-evolutionary process for millions of years, and they play an essential role in the maintenance of host homeostasis. There is accumulating evidence that an imbalance in the gut microbial communities, referred to as dysbiosis, is associated with human pathologies including cardiovascular diseases. We and others have recently demonstrated that heart failure is associated with gut microbiota dysbiosis using 16S ribosomal RNA gene sequencing of fecal samples from patients with heart failure. This finding suggests a potential significance of gut microbiota in the pathophysiology of heart failure. However, the link between the gut microbiota and the heart remains largely unclear. Hypothesis: We hypothesized that manipulation of gut microbiota influences the structure of the heart. Methods: To determine the effects of gut microbiota depletion, cardiac structure and gene expression were evaluated in mice following treatment with orally administered broad-spectrum antibiotic cocktail. We subsequently explored the effects of administration of a single antibiotic agent on myocardial structure. Results: Antibiotic cocktail-treated mice showed a remarkable decrease in myocardial mass and cardiomyocyte size as compared with untreated mice (mean [±SD] ratio of heart weight to body weight, 3.87±0.25 mg/g in 44 antibiotic-treated mice vs. 4.38±0.21 mg/g in 45 untreated mice). The decrease in myocardial mass was associated with substantial changes in gene expression profiles in the heart, including the expression of genes encoding sarcomere proteins and extracellular matrix proteins. In addition, oral treatment with ampicillin alone led to a significant decrease in myocardial mass (mean [±SD] ratio of heart weight to body weight, 3.52±0.24 mg/g in 11 ampicillin-treated mice vs. 4.10±0.24 mg/g in 12 untreated mice). Conclusions: These results suggest that gut microbiota may modulate myocardial mass through the remote regulation of gene expression in the heart. Our study indicates an intimate relationship between the gut microbiota and the heart, and suggests the potential efficacy of manipulating gut microbiota in the prevention and treatment of heart failure.