When we think about heart health, the gut probably isn’t the first thing that comes to mind. However, new research is shedding light on how the trillions of microorganisms living in our digestive tract—collectively known as the gut microbiome—may play a surprising role in cardiovascular disease (Zhang, Y. et al., 2022).
Cardiovascular Disease: The World’s Deadliest Threat
Cardiovascular disease (CVD), is an umbrella term for conditions affecting the heart and blood vessels, including coronary artery disease (CAD), stroke and high blood pressure. These conditions are the leading cause of death worldwide, with heart attack and stroke being responsible for 85% of these deaths (World Health Organization, 2021). While many factors contribute to CVD, including diet, lifestyle, and genetics, scientists are discovering that the composition of our gut microbiome might also be a key player (Zhang, Y. et al., 2022).
The Gut Microbiome: A New Player in Heart Disease
The gut microbiome is a collection of trillions of microbes that reside in the digestive system (Astudillo, A., & Mayrovitz, H., 2021). These microorganisms play essential roles in digestion, nutrient absorption, and immune regulation (Krajmalnik-Brown, 2012). An imbalance in the microbiome, known as dysbiosis, has been linked to various diseases, including inflammatory bowel disease, diabetes, obesity, and now, cardiovascular disease (Kim, 2015).
In recent years, studies have shown that people with heart disease often have different gut microbiomes compared to healthy individuals (Astudillo, A., & Mayrovitz, H., 2021). For example, patients with coronary artery disease tend to have lower levels of Bacteroidetes and higher levels of Lactobacillales. Similarly, those with atrial fibrillation, an irregular heart rhythm, show an overgrowth of bacteria like Ruminococcus and Streptococcus (Zhang, Y. et al., 2022). However, whether these microbial changes cause heart disease or are merely a side effect has been unclear—until now.
The Big Question: Is the Microbiome a Cause of Heart Disease?
The key question scientists have been grappling with is whether changes in the gut microbiome actually cause cardiovascular diseases, or if they simply reflect the body’s response to other heart disease related factors, like diet, age, or genetics.
To explore this, Zhang et al. (2022) used an advanced technique called Mendelian randomization (MR). This method helps to determine if the gut microbiome causes cardiovascular disease by studying natural genetic differences found in the human population. By examining these differences, researchers can infer whether certain gut bacteria might be directly involved in heart disease.
The study uncovered fascinating links between specific bacteria in the gut and different forms of cardiovascular disease. Oxalobacter, a type of bacteria known for breaking down oxalate (a compound that binds to minerals like calcium), was associated with an increased risk of coronary artery disease (CAD). CAD occurs when the coronary arteries, which supply the heart with blood, become narrowed or blocked. Oxalobacter breaking down oxalate in the gut might free up calcium, allowing it to enter the bloodstream. Excess calcium in the blood can contribute to vascular calcification, where calcium deposits build up in the blood vessels, making them stiff and increasing the risk of heart disease (Anderson, J. and Klemmer, P., 2013).
On the flip side, Clostridiaceae, a family of bacteria, was found to be associated with a reduced risk of stroke, particularly ischemic stroke, which occurs when a blood clot blocks blood flow to the brain. This protective effect might be linked to the ability of Clostridiaceae to lower blood pressure and produce short-chain fatty acids, particularly butyrate. Short-chain fatty acids are beneficial compounds that help regulate inflammation and maintain the integrity of the gut barrier. Butyrate specifically has been shown to have neuroprotective effects, which could help reduce damage to the brain during a stroke (Zhang, Y. et al., 2022).
Figure 1. A graphical representation of how Oxalobacter and Clostridiaceae influence risk of of Cardiovascular disease. Image created by Aleutia Peters.
Testing the Connection: The Role of Blood Pressure
The researchers then tested whether these effects could be explained by blood pressure. When they adjusted the data for systolic and diastolic blood pressure, the associations between Oxalobacter and CAD, and Clostridiaceae and stroke, became less significant. This suggests that the gut microbiome might affect cardiovascular disease partly by influencing blood pressure, although more research is needed to confirm this.
The Potential Impact of These Findings
These findings suggest that certain bacteria in the gut could play a direct role in heart disease, either by promoting or protecting against conditions like CAD and stroke. While this study is a step forward, it’s important to remember that the gut microbiome is incredibly complex, and many factors—diet, lifestyle, medication use—can influence its composition.
However, the implications are exciting. If further research confirms these causal links, it could open up new possibilities for preventing and treating heart disease by modifying the gut microbiome. For example, probiotics or prebiotics could be used to encourage the growth of beneficial bacteria like Clostridiaceae, or to reduce harmful bacteria like Oxalobacter.
Looking Ahead: What’s Next?
While the study provides valuable insights, it’s just the tip of the iceberg. Future research could explore how bacteria like Oxalobacter and Clostridiaceae influence specific metabolic pathways, inflammation, and interactions with the immune system. Longitudinal studies, studies that follow people over time, could be used to track the microbiome as people develop heart disease. By collecting data at multiple time points, researchers can determine whether changes in the gut microbiome precede or follow cardiovascular events, providing insight into causal relationships.
Why This Matters for You
Understanding the role of the gut microbiome in heart disease has the potential to revolutionize how we approach heart health. It suggests that maintaining a healthy gut isn’t just about digestion—it could also be key to protecting your heart. As the field of microbiome research continues to grow, we may eventually see new therapies aimed at balancing the gut’s microbial population as part of a broader strategy for preventing and managing cardiovascular disease.
Further Reading:
The paper that this post discussed was from Zhang et al., 2022. The DOI for this paper is as follows: https://doi.org/10.3389/fcvm.2022.971376
For more in depth information on this topic, please refer to the original paper. For further information on the human microbiome, how it may relate to cardiovascular health and its impacts on the human body, please consider these additional sources!
Health and disease markers correlate with gut microbiome composition across thousands of people DOI: https://doi.org/10.1038/s41467-020-18871-1
For some basics on the human microbiome, check out this video!
Citations:
Anderson, J. and Klemmer, P. (2013). Risk of High Dietary Calcium for Arterial Calcification in Older Adults. National Library of Medicine. DOI: https://doi.org/10.3390/nu5103964
Astudillo, A., & Mayrovitz, H. (2021). The gut microbiome and cardiovascular disease. Cureus. DOI: https://doi.org/10.7759/cureus.14519
Chaudhry, R. (2022). Physiology, Cardiovascular. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK493197/
Chen, L., Wang, D., Garmaeva, S., Wijmenga, C., Zhernakova, A., & Fu, J. (2021). The Long-Term Genetic Stability and Individual Specificity of the Human Gut Microbiome. Cell. DOI: https://doi.org/10.1016/j.cell.2021.03.024
Hu, C.-T., Shao, Y.-D., Liu, Y.-Z., Xiao, X., Cheng, Z.-B., Qu, S.-L., Huang, L., & Zhang, C. (2021). Oxidative stress in vascular calcification. Clinica Chimica Acta. DOI: https://doi.org/10.1016/j.cca.2021.04.012
Kim, A. (2015). Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. Clinical Gastroenterology. DOI: https://doi.org/10.1097/MCG.0000000000000356
Krajmalnik-Brown, R., Ilhan, Z.E., Kang D.W., DiBaise, J. (2012). Effects of Gut Microbes on Nutrient Absorption and Energy Regulation. National Library of Medicine. DOI: https://doi.org/10.1177/0884533611436116
Lopez, E., Ballard, B., Jan, A. (2023). Cardiovascular disease. U.S. National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/30571040/
Manor, O., Dai, C., Kornilov, S., Smith, B., Price, N., Lovejoy, J., Gibbons, S., & Magis, A. (2020). Health and disease markers correlate with gut microbiome composition across thousands of people. Nature News. DOI: https://doi.org/10.1038/s41467-020-18871-1
Ogunrinola, G., Oyewale, J., Oshamika, O., & Olasehinde, G. (2020). The Human Microbiome and its Impacts on Health. Wiley Online Library. DOI: https://doi.org/10.1155/2020/8045646
Stoeva, M. K., Garcia-So, J., Justice, N., Myers, J., Tyagi, S., Nemchek, M., McMurdie, P. J., Kolterman, O., & Eid, J. (2021). Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut microbes. DOI: https://doi.org/10.1080/19490976.2021.1907272
World Health Organization. (2021). Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
Zhang, Y., Zhang, X., Chen, D., Lu, J., Gong, Q., Fang, J., & Jiang, J. (2022). Causal Associations Between Gut Microbiome and Cardiovascular Disease: A Mendelian Randomization Study. Frontiers. DOI: https://doi.org/10.1038/s41467-020-18871-1
This blog post includes structure and organization supported by ChatGPT, an AI model developed by OpenAI.
Part of the in-text image obtained from Servier Medical Art – Ischemic Stroke