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FIT Insights

The way to your heart is through the gut:

Cardiovascular health and the microbiome

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in the developed world, and the more we learn about how our native inhabitants predispose us to or protect us from, this disease pathology is of paramount importance. A number of studies have proven that gut microbiota interacts with the host through many pathways, including the trimethylamine (TMA)/trimethylamine N-oxide (TMAO) pathway, small chain fatty acids (SCFAs) pathway, and primary and secondary bile acid (BA) pathways. This article will summarize some of the progress being made in the field, primarily using data comprised in the Circulation paper, Gut Microbiota in Cardiovascular Health and Disease.1

We know that the human body is colonized by trillions of bacteria, archaea, viruses, and unicellular eukaryotes. These organisms play as large a role in overall health as any organ and often interplay with them. Our microbiota, as they’re referred to, metabolize nutrients via primarily anaerobic means in our intestinal tract; the most common are the anaerobes Bacteroidetes and Firmicutes. Our understanding of how these microbes affect our cardiovascular health is evolving as research and technology advances.

Atherosclerosis. We know that atherosclerotic plaques contain bacterial DNA, and the same bacteria can be found colonizing the host’s intestinal tract.2 Metagenomic sequencing of stool microbiota has shown a capacity of the microbiome to promote systemic inflammation and reduce anti-inflammatory/antioxidant carotenes.3 Prolonged systemic inflammation leads to the development of atherosclerosis in the medium- and large-sized vessel through cumulative endothelial dysfunction. This role of the microbiome in the development of atherosclerotic cardiovascular disease (ASCVD) is further corroborated by rodent model studies showing species of Lactobacillus when injected into hosts, are associated with a reduction in infarct size and improved left ventricular function after myocardial infarction (MI).4-5 This prompts us to consider the use of probiotics in modulating ASCVD and recovery of myocyte function after MI.

Hypertension. This is the most modifiable risk factor in the primary prevention and progression of CVD. Studies of rodents with hypertension (HTN) provide us with clues as to how gut microbiota influence the propagation of disease. Intestinal analysis of rodents with HTN show decreases in microbial richness, diversity, evenness, and even increases in the Firmicutes/Bacteroidetes ratio when compared to normotensive rats.6 This supports the notion that a dysfunctional microbiome plays a role in the development of HTN and resistance to conventional antihypertensive therapy. One could theorize that intestinal bacteria, through the pathways mentioned earlier, promote sympathetic activation and vascular dysfunction. A beneficial role for Lactobacillus probiotics in blood pressure regulation has been reporte, and a meta-analysis recently demonstrated a significant decrease in blood pressure in patients treated with probiotics.7-8

Obesity and Type 2 diabetes. The association between obesity and the development of insulin resistance is well-studied. Therapies target several metabolic and digestive enzymes and the administration of exogenous insulin itself. Diabetes has a profound correlation to CVD, and research into how the gut microbiome interacts with these processes is ongoing. One study using fecal microbiota transplantation (FMT) from lean donors to insulin-resistant patients with metabolic syndrome demonstrated lean patients had enhanced numbers of butyrate-producing bacteria.9 The Firmicutes to Bacteroidetes ratio in these patients is elevated, revealing the potential mechanism by which obesity contributes to the development of diabetes. Bariatric surgery has further expanded our knowledge of this phenomenon. Many studies have proven that a change in gut flora occurs after such procedures. One, in particular, found that mice that received a fecal transplant from people who had undergone bariatric surgery gained less fat than did mice that were colonized by microbiota from obese people.10 The BA pathway seems to be the most prominent means by which alterations in the gut microbiome modulate the recovery of insulin sensitivity in obese patients with diabetes after bariatric surgery.

Clearly, human microbiota play a significant role in our wellbeing and the development of many common pathological processes. However, our knowledge of how these bacteria communicate with metabolic enzymes, and the like, is still lacking. Tang, et al. perform an extensive literature review of nearly 200 papers to provide us with a comprehensive review of how the gut is truly the way to a human’s heart. I encourage all those reading this to review this publication as it has the potential to spark novel approaches to treating and preventing CVD in this age of great biotechnological advancement.


Adedapo Iluyomade, MD, MBA

Dapo Iluyomade MD, MBA, is a Cardiovascular Disease Fellow at the University of Miami Miller School of Medicine and Jackson Memorial Hospital in Miami, Fla. His interests pertain to preventive cardiology, cardiovascular outcomes research and healthcare administration. He was formerly a chief resident at the Icahn School of Medicine at Mount Sinai in New York, N.Y.


  1. Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120:1183–96.
  2. Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Bäckhed F. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci 2011;108(suppl 1):4592–4598. doi: 10.1073/pnas.1011383107.
  3. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ ncomms2266.
  4. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Ra ee P, Gross GJ, Salzman NH, Baker JE. Intestinal microbiota determines severity of myo- cardial infarction in rats. FASEB J. 2012;26:1727–1735. doi: 10.1096/ fj.11-197921.
  5. Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, Sidaway JE, Martin G, Gloor GB, Swann JR, Reid G, Karmazyn M. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7:491– 499. doi: 10.1161/CIRCHEARTFAILURE.113.000978.
  6. Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, ?Mohamadzadeh M. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65:1331–1340. doi: 10.1161/HYPERTENSIONAHA.115.05315.
  7. Gómez-Guzmán M, Toral M, Romero M, Jiménez R, Galindo P, Sánchez M, Zarzuelo MJ, Olivares M, Gálvez J, Duarte J. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326–2336. doi: 10.1002/mnfr.201500290.
  8. Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: a systematic review and meta-analysis of random- ized, controlled trials. Hypertension. 2014;64:897–903. doi: 10.1161/ HYPERTENSIONAHA.114.03469.
  9. Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–916.
  10. Tremaroli V, Karlsson F, Werling M, Ståhlman M, Kovatcheva-Datchary P, Olbers T, Fändriks L, le Roux CW, Nielsen J, Bäckhed F. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228–238. doi: 10.1016/j.cmet.2015.07.009.