Gut Microbiota & Cardiovascular Disease

Research on the microbiome has increased significantly in recent years, looking at its many functions in health and immunity.  There is greater recognition of the central role of the gut microbiota in chronic disease, particularly autoimmunity, obesity and metabolic dysfunction.  Now researchers are examining cardiovascular disease (CVD) and its connection to the microbiota.

The Gut Microbiota Role in CVD Risk

Several mechanisms are being investigated, for interactions between the gut, the heart and blood vessels:

  • The microbiota generate certain microbial-associated molecular patterns (MAMPs).  As MAMPs activate the immune system, leading to inflammation, the lining of the blood vessels is damaged.  
  • The microbiota organisms produce short-chain fatty acids (SCFAs) which are used by the heart.  A disruption of microbiota (as occur with antibiotics and pesticides) leads to a lack of SCFAs.
  • Certain microbiota produce trimethylamine N-oxide (TMAO), which increases thrombosis and platelet activation.  The microbiota produce more or less TMAO depending on the individual’s diet.
  • Intestinal permeability increases from a variety of causes.  When this occurs, byproducts of the gut microbiota pass into general circulation, causing inflammation.  Pathogenic bacteria also may translocate to heart tissue.

Current Research on CVD and Microbiota

A meta-analysis performed by an Italian, American and Swiss research team examined the connection between the gut microbiota and cardiovascular health.  The data included 17 clinical studies and more than 26,000 people were followed for 4 to 5 ½ years. The research used a biomarker, TMAO, which is produced by certain gut microbiota and associated with atherosclerosis.  The results showed a positive association between elevated TMAO and mortality from all causes. The researchers also performed subgroup analyses and found the same outcome.

Another study of TMAO, funded by the NIH, compared the TMAO levels in 4,000 patients with the occurrence of major cardiovascular event (stroke, heart attack or death).  The participants were divided into 4 groups, based on their TMAO level. The group with the highest TMAO level had more than doubled risk of a major event compared with the group having the lowest TMAO level.

Researchers in China conducted a stool analysis to characterize the microbiota of people with cardiovascular disease (CVD) and atherosclerosis. Using DNA to determine the organisms present, they found a reduction in the Bacteroides group with increased Enterobacteriaceae and Streptococcus species. These results are associated with an inflammatory gut microbiome, compared with healthy samples.  Particular species were found to be depleted in the CVD samples: F. prausnitzii and Roseburia. F. prausnitzii and Roseburia are also depleted in people with obesity. These bacteria produce butyrate, a short chain fatty acid with a protective role in the gut and beyond. See our article on Bacillus for more on gut microbiota diversity.

A study of over 3 million U.S. veterans, tracked for 7 years, compared data on constipation, heart disease, stroke and death from any cause.  The data showed a higher incidence of heart disease, stroke and all-cause mortality in those who were constipated. Constipation is another indicator of microbiota imbalance.

Cultivating Gut Microbiota for Heart Health

by Jessica Lewis at Pexels

A major determinant of gut microbiota composition and function, is diet. The microbiota change in response to what we eat. In fact, researchers use a high fat diet or “Western” diet (corn,dairy,sucrose), to induce atherosclerosis and systemic inflammation in rodent studies. Our food choices feed the gut microorganisms, such that certain organisms are favored by intake of fruits and vegetables, while other organisms thrive on dairy and meat. Red meat consumption has been associated with cardiovascular disease.  Now, research demonstrates that the level of TMAO produced by the gut microbiota is influenced by meat intake. Preliminary research indicates that people following a vegan or vegetarian diet have lower levels of TMAO. Bottom line for people on an omnivore diet: pile the plate with vegetables and keep red meat servings small and occasional.

Another dietary factor affecting TMAO is resveratrol.  It is known as a free radical scavenger and protective agent of the endothelium (blood vessel lining).  Studies in animals show resveratrol altering the gut microbiota, leading to lower TMAO. Clinical studies in humans have been small and show inconsistent results using resveratrol supplements.  Given its anti-oxidant effects, we recommend food sources of resveratrol: organic grapes, berries, dry roasted unsalted peanuts with skins.

by Marta Branco at Pexels

Loma Linda published a large review of diet and cardiovascular disease, finding those who consumed nuts regularly had a greatly decreased risk of CVD and myocardial infarction. They analyzed data for thousands of participants.  Those with the lowest risk ate nuts 5 or more times per week. For the best nutrition and avoidance of inflammatory oils and excess salt, we recommend raw pecans, walnuts, hazelnuts, almonds, pistachios, macadamia nuts. Almond meal is an option for baking, where the almonds with the skin are ground into flour.  Nuts are very calorie dense, so a serving is just ¼ cup.

Heart Disease – Did you know it’s the leading cause of death for women in U.S.?

To learn more about this critical issue, join Dr Mark Menolascino, MD for the Women’s Heart Health Summit, starting February 4th.  Dr. Mark and other experts reveal how heart disease is expressed differently in women, and as such it must be diagnosed and treated accordingly.  Receive Dr. Mark’s free e-guide when you register.

Sources:

The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease. Eur J Immunol. 2018 Apr;48(4):564-575. doi: 10.1002/eji.201646879. Epub 2018 Jan 19

Impact of the gut microbiome in cardiovascular and autoimmune diseases. Clin Sci (Lond). 2018 Nov 19;132(22):2387-2389. doi: 10.1042/CS20180410.

Impact of Gut Microbiota on Obesity, Diabetes, and Cardiovascular Disease Risk. Curr Cardiol Rep. 2015 Dec;17(12):120. doi: 10.1007/s11886-015-0671-z.

Loss of Gut Microbiota Alters Immune System Composition and Cripples Post-Infarction Cardiac Repair  Circulation. 2018 Oct 8. doi: 10.1161/CIRCULATIONAHA.118.035235. [Epub ahead of print]

Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Eur Heart J. 2017 Oct 14;38(39):2948-2956. doi: 10.1093/eurheartj/ehx342.  

Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.

The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017 Oct 10;8(1):845. doi: 10.1038/s41467-017-00900-1.

Constipation and risk of death and cardiovascular events.  Atherosclerosis. 2018 Dec 23;281:114-120. doi: 10.1016/j.atherosclerosis.2018.12.021

Association Between Dietary Factors and Mortality From Heart Disease, Stroke, and Type 2 Diabetes in the United States. JAMA. 2017 Mar 7;317(9):912-924. doi: 10.1001/jama.2017.0947.

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145

Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota. MBio. 2016 Apr 5;7(2):e02210-15. doi: 10.1128/mBio.02210-15.

Nuts and coronary heart disease: an epidemiological perspective. Br J Nutr. 2006 Nov;96 Suppl 2:S61-7.

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