From Your Gut to Your Heart: The Surprising Role of Exercise in Cardiac Recovery

Background:

The gut microbiome plays a crucial role in maintaining human health by interacting with host metabolism, immune function, and disease states. The diverse microbial communities within our gut not only contribute to digestion and nutrient absorption but also produce various metabolites (small molecules created when the body breaks down food and other substances) that influence overall health of the body. Who knew that a heart-healthy life might start with some gutsy friends in our microbiome? As exercise continues to grow in popularity as part of a healthy lifestyle, interest is also growing in understanding how it affects health beyond fitness. 

Recent studies have examined how exercise impacts the gut microbiome (Lambert et al., 2015; Motiani et al., 2020) as well as how these microbiome changes may influence cardiovascular health, showing that exercise can modify gut microbiota composition and potentially offer protective effects against cardiovascular conditions (Longoria et al., 2022; Zhou et al., 2022). Understanding the mechanisms behind these relationships could lead to new therapeutic approaches aimed at treating cardiovascular health complications.

Myocardial infarction, commonly known as a heart attack, is a leading cause of mortality and morbidity worldwide. Those who survive a heart attack may face chronic heart failure or even premature death, significantly impacting their longevity and overall quality of life. While mild exercise is widely recommended for patients recovering from heart attack, the underlying mechanisms of its benefits remain incompletely understood. Cardiac rehabilitation programs incorporating exercise are known to improve cardiac function, reduce the risk of recurrent events, and enhance overall quality of life. However, it remains unclear exactly how exercise provides these benefits at both the cellular and microbial levels.

Emerging evidence suggests the gut microbiome not only influences the body’s response to exercise but may be especially important for cardiovascular health—a promising new area of research. Alterations in the gut microbiome have been linked to various diseases, including obesity, diabetes, hypertension, and heart disease (Kinross et al., 2011; Ridaura et al., 2013; Lambert et al., 2015). Exercise has been shown to beneficially modulate the gut microbiome, increasing microbial diversity and promoting the growth of beneficial bacteria (Lambert et al., 2015; Motiani et al., 2020; Dalton et al., 2019).”

Central Question:

Yet, an intriguing question remains: can these shifts in the gut microbiome truly impact heart health, especially after a heart attack?

Evidence:

This study by (Zhou et al., (2022) set out to uncover the answer to this question by examining if the gut microbiome plays a role in mediating the cardiac recovery benefits of exercise following a heart attack, using mice as a model for the study. 

This study offers compelling evidence that the recovery and protective benefits of exercise on cardiac health following a heart attack are closely linked to changes in the gut microbiome. For their experiment, the researchers divided the mice into two main groups: an experimental group that underwent a heart attack (myocardial infarction, or MI) and a control group that underwent a “sham” surgery, which involved the surgical procedure without actually inducing a heart attack. All mice were fed the same diet, ensuring that food differences did not affect the results. Within each group, the mice were further divided into exercise and sedentary subgroups, creating four total groups for comparison. The results showed that exercise significantly improved heart function in the heart attack mice. This was reflected in higher ejection fraction (EF) and fractional shortening (FS) scores. EF is a measure of how much blood the heart pumps with each beat, while FS indicates how effectively the heart’s muscle contracts to push that blood out. Together, these measures provide a clear picture of how well the heart is functioning. Additionally, the heart attack (MI) mice that exercised showed less scarring in the heart, improved heart structure, and enhanced endurance compared to the sedentary MI mice. These improvements were also evident when comparing the exercised MI mice to the sham group that did not experience a heart attack, further highlighting the significant protective effects of exercise on heart health in post-heart attack recovery.

Figure 1: Mice Group Design: Diagram illustrating the four groups used in the study design. (Diagram created by the author, Andrew Lawrason)
Figure 2: Comparison of microbial communities between heart attack mice with exercise (MI+Run) and without exercise (MI+Control), showing a distinct difference in microbial composition in exercised mice relative to non-exercised mice. (Figure 2D from Zhou et al. 2022)

Next, the researchers analyzed the gut microbiota—the collection of bacteria living in the gut—using DNA sequencing. They found that exercise caused significant changes in the variety and structure of microbial communities, including increases in beneficial bacteria like Alistipes and Ruminococcus. It’s almost like their gut bacterial composition is getting in shape right along with them! Alistipes is a genus of bacteria that supports gut health by producing anti-inflammatory compounds and short-chain fatty acids, which help regulate immune responses and promote overall metabolic health (Parker et al., 2020). Likewise, Ruminococcus bacteria are key players in the gut ecosystem, breaking down complex carbohydrates into nutrients for the host, thereby supporting gut health and metabolic function (La Reau & Suen, 2018). These alterations in the gut microbiome were statistically associated with improved cardiac health outcomes, suggesting a connection between exercise-induced changes in gut bacteria and enhanced heart function.

To confirm the role of the gut microbiome in improving cardiac function after a heart attack, the researchers used an antibiotic cocktail to significantly lower the number and variety of gut bacteria in heart attack induced mice that had undergone exercise. With this reduction in microbial diversity, they tested whether exercise alone could still provide cardiac benefits, ultimately finding that, without a diverse microbiome, these benefits of exercise were eliminated. They then performed fecal transplant, transferring the gut bacteria from exercised heart attack mice to non-exercised heart attack mice. This process restored cardiac function in the non-exercised mice, confirming the gut microbiome’s involvement in the exercise benefits. The researchers found two beneficial metabolites in the feces, 3-HPA and 4-HBA, of exercised mice that helped improve heart function and protect against damage after a heart attack. These metabolites were then supplemented into the heart attack-induced mice that did not undergo exercise. The results showed that adding these metabolites offered improvements in cardiac function similar to those seen with exercise, as indicated by correspondingly improved EF and FS scores, providing further evidence that gut bacteria promoted by exercise are key players in mediating its positive effects on heart health.

Figure 3: Fecal and Metabolite Transplants: Diagram illustrating the fecal and metabolite transplants from exercised MI mice to sedentary MI mice. (Diagram created by the author, Andrew Lawrason)

Overall, this study reveals a promising connection between exercise, gut health, and heart recovery. While these findings are still in their early stages, they open the door to innovative treatment strategies for cardiovascular health based on gut microbiome composition and exercise. Turns out, ‘no guts, no glory’ isn’t just a saying—it may be a  prescription for a healthier heart in the future!

Your Questions:

Can these findings be translated to humans? While the study offers compelling evidence in mice, it remains unclear how applicable these results are to human physiology. Conducting clinical trials with human participants would be the next logical step in discovering the effects of gut microbiome changes through exercise on cardiac health after a heart attack.

What is the role of diet in enhancing these exercise-induced effects? Exploring whether specific diets can amplify the benefits of exercise on the gut microbiome and heart health would be very interesting and potential treatment plans for patients after a heart attack.

How do different types of exercise aerobic (running/cycling), resistance training (weightlifting), yoga, ect. impact gut microbiomes in treating cardiac health after a heart attack? What about a mixed regimen of both aerobic and resistance training?

Could these metabolites be developed as future supplements or drugs for heart attack patients? I believe these metabolites have potential as future supplements or drugs since they replicate the protective effects of exercise on the heart. If further research confirms their safety and effectiveness in humans, they could become a valuable tool for helping patients recover after a heart attack, especially those unable to exercise.

Further Reading

The Interplay between Cardiovascular Disease, Exercise, and the Gut Microbiom by Candace R. Longoria, John J. Guers, and Sara C. Campbell. doi: 10.31083/j.rcm2311365.

This article dives  into the intricate connections between exercise, gut health, and cardiovascular disease. It highlights how exercise-induced changes in the gut microbiome may help protect against heart disease, offering insights into the therapeutic potential of exercise for cardiovascular health.

Microbiome and Cardiovascular Disease Biomarkers – Stanley Hazen (Video)

Dr. Stanley Hazen explores the connection between the gut microbiome and cardiovascular disease biomarkers, focusing on bacterial metabolites linked to heart disease risk. This video offers an overview of the microbiome’s role in cardiovascular health and emerging microbiome-based strategies for prevention.

Exercise Influence on the Microbiome-Gut-Brain Axis by A. Dalton, C. Mermier, and M. Zuhl. doi: 10.1080/19490976.2018.1562268.

This review examines the effects of exercise on the microbiome-gut-brain axis, showcasing the wide-reaching impacts of exercise on microbial diversity and brain function. It explores the interconnected roles of exercise, gut health, and mental well-being.

Influence of Diet on the Gut Microbiome and Implications for Human Health by R.K. Singh, H.W. Chang, D. Yan, et al. doi: 10.1186/s12967-017-1175-y.

This study investigates how dietary habits shape the gut microbiome and overall health. It reveals the crucial role diet plays in maintaining a balanced microbiome and reducing disease risk, complementing the benefits seen with exercise

Resistance and Endurance Exercise Training Induce Differential Changes in Gut Microbiota Composition in Murine Models by J. Fernández, M. Fernández-Sanjurjo, E. Iglesias-Gutiérrez, et al. doi: 10.3389/fphys.2021.748854.

This article compares the effects of resistance and endurance training on gut microbiota composition in mice, showing that different exercise types uniquely impact microbial diversity. Readers looking to understand how various forms of exercise influence gut health will gain new perspectives from this research.

References: 

Lambert JE, Myslicki JP, Bomhof MR, Belke DD, Shearer J, Reimer RA. Exercise training modifies gut microbiota in normal and diabetic mice. Applied Physiology, Nutrition, and Metabolism. 2015;40(7):749-752. doi: 10.1139/apnm-2014-0452.

Motiani KK, Collado MC, Eskelinen JJ, Virtanen KA, Löyttyniemi E, Salminen S, Nuutila P, Kalliokoski KK, Hannukainen JC. Exercise training modulates gut microbiota profile and improves endotoxemia. Medicine & Science in Sports & Exercise. 2020;52(1):94-104. doi: 10.1249/MSS.0000000000002112.

Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. doi: 10.1126/science.1241214.

Dalton A, Mermier C, Zuhl M. Exercise influence on the microbiome-gut-brain axis. Gut Microbes. 2019;10(5):555-568. doi: 10.1080/19490976.2018.1562268.

Zhou Q, Deng J, Pan X, et al. Gut microbiome mediates the protective effects of exercise after myocardial infarction. Microbiome. 2022;10:82. doi: 10.1186/s40168-022-01271-6.

Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. The genus Alistipes: gut bacteria with emerging implications to inflammation, cancer, and mental health. Frontiers in Immunology. 2020;11:906. doi: 10.3389/fimmu.2020.00906.

La Reau AJ, Suen G. The Ruminococci: key symbionts of the gut ecosystem. Journal of Microbiology. 2018;56(3):199-208. doi: 10.1007/s12275-018-8024-4.

Longoria CR, Guers JJ, Campbell SC. The interplay between cardiovascular disease, exercise, and the gut microbiome. Reviews in Cardiovascular Medicine. 2022;23(11):365. doi: 10.31083/j.rcm2311365.

Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine. 2017;15(1):73. doi: 10.1186/s12967-017-1175-y.

Fernández J, Fernández-Sanjurjo M, Iglesias-Gutiérrez E, Martínez-Camblor P, Villar CJ, Tomás-Zapico C, Fernández-García B, Lombó F. Resistance and endurance exercise training induce differential changes in gut microbiota composition in murine models. Frontiers in Physiology. 2021;12:748854. doi: 10.3389/fphys.2021.748854.

Kinross JM, Darzi AW, Nicholson JK. Gut microbiome-host interactions in health and disease. Genome Medicine. 2011;3:14. doi: 10.1186/gm228.

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