Healthy gut, healthy heart

Health and Wellness 27. mar 2022 4 min Professor of Human Metabolism, Chief Research Physician, Specialist of Endocrinology Oluf Borbye Pedersen Written by Kristian Sjøgren

New research clearly identifies the association between a healthy gut and cardiovascular health. People should look after their gut microbiome to strengthen their heart, says a researcher.

Many people whose gut microbiome has unhealthy composition and function have heart problems.

This is the conclusion of a new study investigating the association between the density, diversity and function of gut bacteria and cardiovascular disease.

The study shows that people with coronary atherosclerosis have fewer health-promoting types of gut bacteria even many years before being diagnosed with heart disease. The rest of their microbiome includes species that promote inflammation and other substances that can cause atherosclerosis.

The researchers also adjusted for confounding factors for the first time, including how pre-existing conditions such as type 2 diabetes and obesity or medicine use affect the gut microbiome.

“The extensive changes in the gut microbiome occur many years before the onset of coronary atherosclerosis. Official initiatives to promote health should therefore also focus more on how to establish and maintain a healthy gut microbiome, since this affects the development of a broad range of major noncommunicable diseases, including cardiovascular disease,” explains Oluf Borbye Pedersen, Clinical Professor of Human Metabolism who conducted the study at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The research has been published in Nature Medicine. Oluf Borbye Pedersen led the research behind one study and co-authored the second article.

1,241 participants

The 10-year project originated through a major European Union research grant to the MetaCardis consortium, in which 63 researchers investigated the association between the myriad bacteria in the gut and cardiovascular health among 1,241 middle-aged people from Denmark, France and Germany.

The participants were divided into four groups:

  • Healthy
  • People with overweight or type 2 diabetes not taking medication
  • People with overweight or type 2 diabetes taking medication
  • People with cardiovascular disease, including heart failure due to coronary sclerosis, angina pectoris or coronary thrombosis

Including four groups of study participants enabled the researchers to eliminate the confounding effects of type 2 diabetes and overweight (which people often have before they are diagnosed with heart disease) and how drugs affect the gut microbiome from the association between cardiovascular disease per se and the gut microbiome.

“This is an experimental design that mimics the natural progression from being healthy to developing disorders in glucose and fat metabolism without diagnosed cardiovascular disease and eventually overt disorders of ischaemic heart disease. This reflects how coronary sclerosis develops over perhaps 30–50 years, and despite the cross-sectional nature of the study design, we can estimate when and how disruption of the gut microbiome occurs at the various stages of disease,” says Oluf Borbye Pedersen.

Although research has repeatedly confirmed that the gut microbiome influences the development of many diseases, researchers have had difficulty separating the effects of overweight and type 2 diabetes from the effects of chronic heart disease, since overweight and diabetes often precede coronary atherosclerosis.

Another study from MetaCardis has also shown the individual and synergistic effects of drugs on the gut microbiome. The researchers wanted to adjust for these confounders in the new study, so they would solely examine the association between the gut microbiome and cardiovascular disease.

Gut microbiome clearly associated with cardiovascular health

The researchers determined the prevalence, variation and function of more than 700 types of gut bacteria, some of which benefit health and others worsen health.

The researchers also examined differences in the concentrations of about 1,500 metabolites in the participants’ blood. The gut bacteria produce many of these.

The results confirmed that people with chronic heart disease had a smaller density and diversity of gut bacteria, which reduces the ability of the gut microbiome to synthesise health-promoting substances that regulate the functions of various organs.

For example, the gut microbiome of people with ischaemic cardiovascular disease were less able to produce butyric acid, a short-chain fatty acid that protects the intestinal wall, is anti-inflammatory and has positive regulatory effects on people’s epigenome.

Conversely, people with coronary sclerosis had increased bacterial production of branched-chain amino acids, which is associated with increased risk of insulin resistance among people with an unhealthy lifestyle and therefore also the development of metabolic syndrome, type 2 diabetes and atherosclerosis.

“These changes in the gut microbiome may occur many years before the diagnosis of ischaemic cardiovascular disease, namely in the precursor disorders, overweight and type 2 diabetes” explains Oluf Borbye Pedersen.

More focused attention on official recommendations on lifestyle

Further examination revealed that the gut bacteria among people with diagnosed chronic heart disease have an increased ability to produce trimethylamine from dietary l-carnitine and choline. The liver converts trimethylamine to trimethylamine oxide, which is associated with increased platelet aggregation.

Trimethylamine oxide also contributes to developing inflammation and is associated with an increased risk of atherosclerosis.

“The results also show that the gut microbiome of people with cardiovascular disease shows an altered capacity for degradation of aromatic amino acids,” says Oluf Borbye Pedersen.

Studies in mice have shown that abnormalities in the metabolism of aromatic amino acids are associated with changes in the structure of blood vessels and the risk of atherosclerosis.

“Thus, the research indicates several possible associations between unhealthy diet, imbalances in the intestinal microbiome and ischaemic artery disorders,” explains Oluf Borbye Pedersen.

The good news

According to Oluf Borbye Pedersen, the results provide additional motivation for adhering to the official recommendations on lifestyle. If you want to improve your cardiovascular health, you should carefully cultivate your gut microbiome.

“The official recommendations on lifestyle are largely based on observational population studies. Our microbiome studies are also observational, but parallel and already published mechanistic experiments on cells and experimental studies in animals elucidating the effects of altered bacterial metabolites among people with coronary sclerosis show the need for action,” says Oluf Borbye Pedersen.

Oluf Borbye Pedersen hopes that this research will motivate more people to follow the official recommendations on lifestyle. Based on animal experiments, the alterations in blood metabolites seem to be associated with the development of cardiovascular disease.

“The good news is that reported interventions on animals and people have shown that the imbalances in the gut microbiome already present in the precursor stages of cardiovascular disease, overweight and type 2 diabetes can be corrected by stopping smoking, daily exercise and eating a varied and predominantly plant-based diet. Much more attention should therefore be given to complement the prevention of chronic heart disease through drugs that counteract high cholesterol and hypertension, obesity and diabetes with an optimised lifestyle that keeps the gut microbiome in great shape,” concludes Oluf Borbye Pedersen.

Microbiome and metabolome features of the cardiometabolic disease spectrum” and “Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease” have been published in Nature Medicine. Oluf Borbye Pedersen is a Clinical Professor at Department of Clinical Medicine, University of Copenhagen and affiliated to the Novo Nordisk Foundation Center for Basic Metabolic Research. He is also Chief Research Physician at Herlev & Gentofte University Hospital.

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