The gut truly extends in action far beyond digestion and heart health is no exception. There are six main ways the health of the gut affects the cardiovascular system. Gut microbiome (stool) analysis and laboratory analysis may help direct treatment in those currently with and at-risk of cardiovascular disease.

GUT-Heart connection

  1. Gut permeability in presence of an overgrowth of gram negative bacteria increases circulation of inflammatory biochemicals.
  2. Trimethylamine N-oxide (a product of digestion) blood elevated levels increase arterial plaque buildup or atherosclerosis.
  3. Phenylacetylglutamine ( PAGIn) is a gut microbiota derived-metabolite that enhances platelet activation and thrombosis
  4. Short chain fatty acids (SCFA),  or “postbiotic” production from microbiome bacterial fermentation of dietary fibre.
  5. Bile acid altered production alters glucose, insulin and lipid metabolism that leads to increased inflammation and risk of CVD. 
  6. Tissue damage. Poor circulation from compromised heart health (CHF), food sensitivity or intolerance, chronic stress, food poisoning, nutrient deficiency, alters mucousal function and exacerbates chronic and cardiovascular disease.

“It all starts in the gut” ~ Hippocrates

Gut permeability

Intestinal barrier function is maintained by physical factors including tight junctions between epithelial (gut lining) cells, mucus production, and mucosal immunity. Impaired barrier function is often observed in heart failure patients. Why? High endotoxin levels, or lipopolysaccharides (LPS), result from gram negative bacterial overgrowth or imbalanced gut microbes, induce body wide release of pro-inflammatory cytokines that trigger chronic inflammatory states body wide, including the heart. An overgrowth of gram negative bacteria is a result of infection, medication, environment and poor dietary habits.

Trimethylamine N-oxide

Dietary precursors, such as choline and carnitine, are metabolized into trimethylamine- oxide (TMAO) by gut microbiota.  High TMAO blood levels is associated with prevalence of cardiovascular disease and increased risk for major adverse cardiac events, including myocardial infarction ( heart attack), stroke or death. Two ways TMAO affects heart health: Firstly, TMAO decreases enzymes that manage bile acid and cholesterol re-circulation. Secondly, TMAO increases risk of blood clot because it increases endoplasmic recticulum calcium release in platelet cell, consequently leading to platelet aggregation and thrombosis.


A gut microbiota-dependent byproduct, phenylacetylglutamine (PAGIn) is responsible for enhanced platelet activation and thrombosis, which increases clot risk. Overgrowth of microbial bacteria like Roseburia, Blautia, and Ruminococcus and PAGln synthesis are observed in corany artery diseased patients. There is an direct association between plasma PAGIn levels patients with cardiovascular disease.

Short chain fatty acids

Probiotics help boost the healthy microbes in the gut. Prebiotics, or dietary fibre, is required to feed the gut bacteria on a daily basis. “Postbiotics”, or short chain fatty acids (SCFAs) are what the microbiome makes when it ferments dietary fibre.

Most North Americans get 5g of fibre a day. The body needs more like 35g a day of combined soluble and insoluble fibre. Lack of dietary fibre and an imbalance in gut microbes reduces the quantity and quality of these postbiotics. This leads to high blood pressure and higher risk of atrial fibrillation. Different strains of bacteria in the gut are related to either a healthy state, or an inflammatory state. A comprehensive microbiome analysis offered by a qualified practitioner is one way to assess the health of your gut microbiome and provides tangible information to direct a course of treatment.

Bile acids

Primary bile acids including chenodeoxycholic acid and cholic acids have distinct effects on cardiac health when compared to secondary bile acids, deoxycholic acid and lithocholic acid. Higher levels of secondary bile acids compared to primary bile acids are found in those with cardiovascular disease compared to healthy controls.

Primary bile acids can work as hormone to decrease triglyceride (TAGs) accumulation, fatty acid oxidation, decrease the expression of pro-inflammatory cytokines and chemokines in aorta through the inactivation of the inflammatory NF-κB.

When there are too many primary bile acids, some escape from the small intestine to the large intestine (now are called secondary bile acids). Healthy levels of secondary bile acids are good. They contribute to glucose balance, increased energy expenditure through activation of thyroid hormones, and in animal models shows anti-inflammatory effects. However, higher ratios of secondary bile acids are linked to increased gut permeability, fatty liver disease, insulin resistance in type 2 diabetes, and cardiovascular and metabolic disease.

  • A healthy balance of gut bacteria and intake of healthy fats helps keep the balance of primary and secondary bile acids.
  • Bile acids are made in the liver and digested by gut microbes.
  • Primary bile acids (PBAs) (those absorbed in the terminal ileum of the small intestine) help maintain intestinal barrier integrity, maintain glucose homeostasis, lipid metabolism, and decrease hepatic inflammation and fibrosis
  • Secondary bile acids are the overflow of primary bile acids into the large intestine.

Tissue damage

Poor circulation from compromised heart health, like in congestive heart failure, starves the mucous membranes of oxygen, damages tissue and ultimately alters mucousal function. Food intolerance or sensitivity, nutrient depletion, imbalanced microbes, food poisoning and infection can all promote gut permeability, lead to endotoxin (LPS) leakage, chronic inflammatory response and further disease development.

Gut health matters. Not only is there a gut-heart axis, there is a gut-skin, gut-brain, gut-liver, and gut-hormone axis too. Health starts with a healthy gut and food is truly our first medicine. Dr. Laura M. Brown, ND has scientifically evidenced-backed protocols that are customized to meet your individual needs. And Dr. Laura is passionate about good gut health, as exampled by her first published book, Beyond Digestion. Follow her on Linked In for frequent posts and shares on the topic #guthealthmatters.


Nemet, I., Saha, P. P., Gupta, N., Zhu, W., Romano, K. A., Skye, S. M., Cajka, T., Mohan, M. L., Li, L., Wu, Y., Funabashi, M., Ramer-Tait, A. E., Naga Prasad, S. V., Fiehn, O., Rey, F. E., Tang, W., Fischbach, M. A., DiDonato, J. A., & Hazen, S. L. (2020). A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. Cell, 180(5), 862–877.e22.

Wang, Z., & Zhao, Y. (2018). Gut microbiota derived metabolites in cardiovascular health and disease. Protein & cell, 9(5), 416–431.

Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020). Gut Microbiota and Cardiovascular Disease. Circulation research, 127(4), 553–570.

Zuo, K., Fang, C., Liu, Z., Fu, Y., Liu, Y., Liu, L., Wang, Y., Yin, X., Liu, X., Li, J., Zhong, J., Chen, M., Xu, L., & Yang, X. (2022). Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling. International journal of biological sciences, 18(10), 4219–4232.