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The Gut Microbiota Mediates the Protective Effects of Spironolactone on Myocardial Infarction
Lu Li1,2, Jian-Yong Sun1,2, Yu-Lin Li1,2
1Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, People's Republic of China.
Insights
Spironolactone’s benefits for myocardial infarction (MI) depend on gut microbiota. Eliminating gut microbes negated spironolactone’s protective effects in mice with MI, highlighting the gut flora’s crucial role in this cardiovascular disease treatment.
Area of Science:
- Cardiovascular Medicine
- Microbiology
- Pharmacology
Background:
- Myocardial infarction (MI) is a leading cause of global mortality and morbidity.
- Spironolactone is a key therapeutic agent for cardiac failure, improving cardiac function post-MI.
- The role of gut microbiota in mediating spironolactone's effects on MI remains unclear.
Purpose of the Study:
- To investigate whether gut microbiota mediates the beneficial effects of spironolactone in a mouse model of myocardial infarction.
- To explore the impact of spironolactone on gut microbiota composition following MI.
Main Methods:
- Utilized male C57BL/6J mice subjected to myocardial infarction (MI) or sham operations.
- Investigated the effects of spironolactone with and without gut microbiota (using microbiota deletion methods).
- Assessed cardiac dysfunction and infarct size.
- Analyzed alterations in gut microbiota composition.
Main Results:
- Deletion of gut microbiota abolished the cardioprotective effects of spironolactone in MI mice, leading to worsened cardiac dysfunction and increased infarct size.
- Spironolactone treatment significantly altered gut microbiota composition in mice after both sham and MI operations.
- Probiotic administration was also explored in the context of MI.
Conclusions:
- Gut microbiota plays a critical role in mediating the therapeutic benefits of spironolactone for myocardial infarction.
- Targeting the gut flora may represent a novel therapeutic strategy for managing MI.
- Spironolactone influences gut microbial composition, suggesting a gut-heart axis interaction in cardiovascular disease.
Abstract:
Myocardial infarction (MI) is a type of cardiovascular disease that influences millions of human beings worldwide and has a great rate of mortality and morbidity. Spironolactone has been used as a critical drug for the treatment of cardiac failure and it ameliorates cardiac dysfunction post-MI. Despite these findings, whether there is a relationship between the therapeutic effects of spironolactone and the gut microorganism after MI has not been determined. In our research, we used male C57BL/6 J mice to explore whether the gut microbiota mediates the beneficial function of spironolactone after myocardial infarction. We demonstrated that deletion of the gut microbiota eliminated the beneficial function of spironolactone in MI mice, displaying exacerbated cardiac dysfunction, cardiac infarct size. In addition, the gut microbiota was altered by spironolactone after sham or MI operation in mice. We also used male C57BL/6 J mice to investigate the function of a probiotic in the myocardial infarction. In summary, our findings reveal a precious role of the gut flora in the therapeutic function of spironolactone on MI.
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