By Emily Watters, Winter 2020.

Heart disease is the leading cause of death for both men and women of all ethnic and racial groups in the United States, with 1 in 4 deaths resulting from heart disease each year [1]. As such, recent research has strived to attack this issue from every angle. The eventual goal with this research is to find a way to increase the quality and effectiveness of preventative healthcare and help those who are already affected by one (or more) of the many variations of cardiovascular disease. The human gut microbiome has recently become a burgeoning research medium for a multitude of diseases and conditions, thus leading to its intersection with cardiovascular disease. 

The Khomtchouk Lab at the University of Chicago seeks to use cardioinformatics to investigate possible causes or future treatments for cardiovascular disease [2]. As a Bioinformatics and Computational Biology Intern, I have spent a lot of time analyzing academic papers that have studied connections between cardiovascular disease and the human gut microbiome. While working in the lab, my eventual goal is to bioinformatically test multiple datasets to answer a hypothesis that questions the intersection between cardiovascular disease and the human gut microbiome. I would also like to eventually create a database that hosts all available published data related to the microbiome and cardiovascular disease. 

This article will serve as a literature review of two papers that sought to find connections between the microbiome and cardiovascular disease. The first paper discusses atherosclerosis, which is a condition that occurs when plaque builds up inside the arteries, causing the arteries to narrow and make it more difficult to breathe. It can lead to a heart attack, stroke, or death, as well as coronary artery disease [3]. In their study, Jie et al. compared the microbiota of 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. They found that the ACVD gut microbiome deviates from the healthy cohort with an increased abundance of Enterobacteriaceae and Streptococcus sp., and smaller amount of Bacteroides and Prevotella. However, there was little difference found in richness (the number of species represented in an ecological community) or diversity between the control and atherosclerosis samples. They also found that a number of bacteria species commonly found in the oral cavity (such as Streptococcus sp. and Lactobacillus salivarius) were also higher in subjects with atherosclerosis than the controls. Ruminococcus gnavus, a bacteria species commonly associated with low gut richness and inflammatory bowel disease, was also found in higher amounts in subjects with atherosclerosis than controls. Perhaps most interestingly, Eggerthella lenta, which has been found to have enzymes for deactivating the cardiac drug digoxin was higher in atherosclerosis samples than the controls [4]. These findings are significant because they distinguished a difference in the microbiome composition of those with atherosclerosis and those without. Specifically, this creates an avenue in which further research is needed, as it could be possible that this imbalance in the microbiome led to atherosclerosis in some way, or it could be possible that atherosclerosis creates changes in the microbiome that lead to deviations from normal.

While the previous study focused on atherosclerosis, this next study focuses on coronary artery disease, which can result after prolonged atherosclerosis. Yoshida et al. analyzed the gut microbiomes of patients with coronary artery disease and healthy controls in order to determine if treatment with any species of live bacteria could possibly help to prevent coronary artery disease. Coronary artery disease can arise from atherosclerosis, as plaque buildup plays a significant role in narrowing coronary arteries, eventually decreasing blood flow to the heart [5]. Fecal samples were collected from two groups—one healthy group and one comprised of subjects with coronary artery disease—and the researchers used 16S ribosomal RNA gene sequencing to reveal a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in the samples of coronary artery disease patients in comparison to the control. Indeed, these results are incredibly interesting, as both Bacteroides vulgatus and Bacteroides dorei have proven to have a protective effect against atherosclerosis. As a result, they were able to conclude that a treatment plan using live Bacteroides vulgatus and Bacteroides dorei in patients could be used to both prevent or alleviate coronary artery disease [6]. This is because—as mentioned—atherosclerosis is a serious condition and can lead to coronary artery disease. So, rebalancing the amount of Bacteroides vulgatus and Bacteroides dorei in a microbiome could slow the progression of atherosclerosis and possibly avoid the opportunity for it to develop into coronary artery disease [7]. 

The results of these studies provide an interesting angle for cardiovascular disease treatment and preventative measures. They present a novel treatment plan utilizing live bacteria to supplement microbiomes that are lacking certain species necessary in a healthy gut microbiome. Although not an entirely new concept, the use of live bacteria is a fascinating proposition for curing conditions that are generally treated with lifestyle changes—such as certain diets or exercise regiments—prescription drugs, and/or medical procedures. While more research/studies could be necessary before live bacterial treatments are given a permanent place in cardiovascular disease treatment, it is certainly intriguing to consider if the future of preventive care and treatment lies in readjusting the human gut microbiome.  

[1] “Heart Disease Facts.” Centers for Disease Control and Prevention. Centers for Disease Control 

[2] Khomtchouk, Bohdan B., et al. 2019 “Cardioinformatics: the nexus of bioinformatics and precision cardiology.” Briefings in Bioinformatics. https://doi.org/10.1093/bib/bbz119

[3] “Atherosclerosis.” National Heart Lung and Blood Institute. U.S. Department of Health and Human Services. https://www.nhlbi.nih.gov/health-topics/atherosclerosis. 

[4] Jie, Zhuye, et al. 2017. “The Gut Microbiome in Atherosclerotic Cardiovascular Disease.” Nature Communications 8. https://doi.org/10.1038/s41467-017-00900-1

[5] Mayo Clinic. 2018. “Coronary Artery Disease.” Mayo Foundation for Medical Education and Research https://www.mayoclinic.org/diseases-conditions/coronary-artery-disease/symptoms-causes/syc-20350613.

[6] Yoshida, Naofumi, et al. 2018. “Bacteroides Vulgatus and Bacteroides Dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis.” Circulation 138, no. 22 (2018): 2486–98. https://doi.org/10.1161/circulationaha.118.033714.

[7] Yoshida, Naofumi, et al. 2019. “Effect of Resistant Starch on the Gut Microbiota and Its Metabolites in Patients with Coronary Artery Disease.” Journal of Atherosclerosis and Thrombosis 26, no. 8 (January 2019): 705–19. https://doi.org/10.5551/jat.47415.