Cardiovascular disease is the leading cause of mortality worldwide and in the United States. In fact, most patients seen by healthcare providers will die of cardiovascular disease (CVD) or a related condition, regardless of the initial reason for their visit. 1 Many factors can increase the risk of developing heart disease, including inactivity, toxic burden and being overweight or obese. But there’s an important factor that may often be overlooked: gut health.

Here are a few questions to keep in mind when considering the gut-heart connection:

  • How many people with CVD also have chronic, systemic inflammation?
  • What is the relationship between CVD and certain dietary habits?
  • How many people with CVD take proton-pump inhibitors (PPIs) because they have also been diagnosed with acid reflux or gastritis?
How the Gut Impacts Heart Health

Poor eating habits, chronic inflammation and PPIs can all lead to disruptions in the gut microbiome and further increase CVD complications. According to a study in Microbiome, gut bacteria-related processes have been tied to a higher risk of congestive heart failure (CHF), atherosclerosis and major cardiovascular events like heart attack and stroke.2

Observations and experiments alike have shown that a shift in an individual’s microbiota can result in profound changes in metabolic function and even biomarkers of cardiometabolic risk. The microbiome also affects blood vessels, and there are 60,000 miles of vasculature in the human body. When we consider lifestyle-based diseases, specifically cardiovascular conditions, even the best nutrition plans have a low chance of clinical success if the vasculature cannot properly bring nutrients from the digestive system to the bloodstream and then cells.

Let’s consider patients diagnosed with heart failure. In this patient population, it has been shown that splanchnic hypoperfusion causes ischemia and intestinal edema.3 It is widely known that ischemia can lead to tissue death and edema can cause decreased elasticity of arteries, veins, joints and muscles. But how is the gut a factor in this?

Splanchnic hypoperfusion also leads to bacterial translocation, which allows bacterial metabolites to enter the blood circulation via a dysfunctional intestinal barrier. This results in further local and systemic inflammatory responses. Therefore, gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including heart failure.3

TMAO Testing for Risk Assessment

The TMAO (or trimethylamine N-oxide) test is an important medical advancement because it allows for measuring the microbiome’s impact on cardiovascular disease. Serum TMAO will only be formed in significant quantities if the bacteria that convert exogenous substances to TMA are present. Emerging evidence also suggests microbial dysbiosis—not dietary choline—is the problem.4 TMAO testing may be used for the following purposes:5

  • To aid in the assessment of risk for CVD, independent of established risk factors
  • To aid in the determination of altered gut microbiome (gut dysbiosis) in individuals who may benefit from intensive dietary intervention
  • To monitor therapy aimed at reducing TMAO concentrations

Additionally, TMAO appears to participate in the pathologic process that leads to heart failure and can even serve as an early warning marker to identify individuals at risk of heart failure progression.3 Most recently, research shows that high blood levels of TMAO were associated with higher rates of premature death in a group of 2,235 patients with stable coronary artery disease. Those found to have higher blood levels of TMAO had a four-fold greater risk of dying from any cause over the subsequent five years.6


Interventions for High TMAO

According to the Cleveland Clinic, some interventions for lowering TMAO include:

  • Minimizing the consumption of full-fat dairy products, including whole milk, egg yolk, cream cheese and butter
  • Minimizing both processed and unprocessed red meat (e.g., beef, pork, lamb and veal)
  • Having a diverse diet rich in plant foods and soluble and insoluble fiber7
  • Supplementation with berberine
  • Probiotics, such as those containing Lactobacilli, have been shown to reduce blood cholesterol levels because some bacteria express the enzyme bile salt hydrolase, which can affect intestinal cholesterol reabsorption8
The Bottom Line

Overall, patients who are impacted by cardiovascular diseases have complex and dynamic needs. That is why care providers must consider a whole-systems approach for these patients. While organs have specific functions, the body works as one, synergistic system, and a single organ may not function optimally if others are impaired. The gut-heart connection is integral when addressing cardiovascular health.


Ioana Manahilova, DC earned her doctorate in chiropractic from the National University of Health Sciences (NUHS) in Lombard, Illinois in 2021. She obtained a bachelor of science degree in human physiology from the University of Iowa. Additionally, she is very involved in research. She was previously awarded a grant for international research to identify the impact of diet on diabetes and she has worked with the MESA study at Northwestern University in Chicago.



  1. National Center for Health Statistics. Leading Causes of Death. January 13, 2022. Accessed June 29, 2022.
  2. Kazemian N, Mahmoudi M, Halperin F, Wu JC, Pakpour S. Gut microbiota and cardiovascular disease: opportunities and challenges. Microbiome. 2020;8(1):36. Published 2020 Mar 14. doi:10.1186/s40168-020-00821-0
  3. Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Transl Res. 2021;228:109-125. doi:10.1016/j.trsl.2020.08.007
  4. Romano KA, Martinez-Del Campo A, Kasahara K, et al. Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption. Cell Host Microbe. 2017;22(3):279-290.e7. doi:10.1016/j.chom.2017.07.021
  5. Labcorp. TMAO (Trimethylamine N-oxide). 2021. Accessed June 29, 2022.,a%20monitor%20therapy%20aimed%20at
  6. Senthong V, Wang Z, Li XS, et al. Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide and 5-Year Mortality Risk in Stable Coronary Artery Disease: The Contributory Role of Intestinal Microbiota in a COURAGE-Like Patient Cohort. J Am Heart Assoc. 2016;5(6):e002816. Published 2016 Jun 10. doi:10.1161/JAHA.115.002816
  7. Cleveland Heartlab. The Gut, the Heart, and TMAO. August 1, 2016. Accessed June 29, 2022.,energy%20drinks%20containing%20choline%2C%20phosphatidylcholine%20(
  8. Taranto MP, Medici M, Perdigon G, Ruiz Holgado AP, Valdez GF. Effect of Lactobacillus reuteri on the prevention of hypercholesterolemia in mice. J Dairy Sci. 2000;83(3):401-403. doi:10.3168/jds.S0022-0302(00)74895-8