High incidence of sudden death? Characteristics of intestinal bacteria in patients with cardiovascular disease

The researchers showed how major disruptions can occur in the gut microbiota of people with heart disease. Given the latest evidence from microbiome research, researchers are now calling for stronger, more targeted public health initiatives to prevent or delay these common diseases, which are the leading causes of premature death worldwide, by encouraging plant-based, energy-controlled diets, avoiding smoking, and adhering to daily exercise.

The human gut contains trillions of species of bacteria, collectively known as the gut microbiome, which can have both positive and negative effects on human health. When in equilibrium, they act like an internal chemical plant, producing large numbers of health-promoting compounds. However, an unhealthy lifestyle — poor diet, smoking, lack of physical activity or disease — can upset this balance, leading to the production of compounds in the microbiome that can trigger a variety of non-communicable chronic diseases in people at high genetic risk, including myocardial infarction, angina, or heart failure.

Scientists have found that the gut microbiota of people with chronic heart disease has changed. They found that compounds produced by the diseased microbiota, for example, trimethylamine (TMA), when modified in the liver of a human host, cause arteriosclerosis.

However, these findings that alter the gut microbiota are challenged because they were made in studies of drug-treated patients. Heart disease patients are given several different medications, each of which alters the gut microbiome. Therefore, it is unclear whether it is the drug or the heart disease itself that causes the imbalance of the gut microbiota of patients with cardiovascular disease.

More serious complications are that heart disease is often accompanied by the development of early overweight and type 2 diabetes, both of which are also characterized by disorders of the gut microbiota. Therefore, it is still necessary to prove whether the imbalance of the intestinal flora is characteristic of the heart disease itself.

Heart disease can cause disturbances in the gut microbiome

To answer these key questions, a consortium of European researchers established the EU-funded MetaCardis research project in 2012 to investigate the role of gut microbes in cardiometabolic diseases. Professor Oluf Pedersen of the University of Copenhagen is one of the leading researchers, and he and his colleagues published their findings in the journal Nature Medicine.

"We took a study design that reflects the onset and growth of heart disease over time, replacing a longitudinal study of the gut microbiota that would otherwise not have been possible because it would take 50-60 years for arteriosclerosis symptoms and heart disease diagnosis to occur." He conducted the research at the Novo Nordisk Centre for Basal Metabolism Research (CBMR) at the University of Copenhagen.

The researchers recruited 1241 middle-aged people from Denmark, France and Germany, including healthy people, people who were obese and had type 2 diabetes but had not been diagnosed with heart disease, as well as patients with myocardial infarction, angina or heart failure. The researchers quantified about 700 different bacterial species and estimated their function in the gut microbiota, comparing these findings to more than 1,000 compounds circulating in the bloodstream, many of which come from chemical plants inside the gut.

Professor Oluf Pedersen said: "We found that about half of these gut bacteria and blood compounds were altered by drug treatment and were not directly related to heart disease or early diseases such as diabetes or obesity that appeared before a heart disease diagnosis."

"Of the remaining half of patients, about 75 percent of gut microbiota disorders occur in the early stages of overweight and type 2 diabetes, many years before patients notice any heart disease symptoms."

However, early changes in the microbiota persist in patients with heart disease, who also exhibit specific changes in the composition and function of the gut microbiota associated with heart disease. Whether in the early stages of metabolic abnormalities or in the late stages of the diagnosis of heart disease, the diseased microbiome is characterized by a loss of bacterial cells and bacterial capacity. In addition, patients showed a decrease in the bacterial species known to produce health-promoting compounds (e.g., short-chain fatty acids), as well as an increase in the number of bacteria that produce unhealthy compounds in the metabolism of certain dietary amino acids, choline and levineine. The analysis of blood compounds reflects an imbalance in the gut microbiota.

A plant-based and energy-controlled diet can help

A study from Israel confirmed and promoted the findings of changes in gut microbiota and blood compounds in patients with acute myocardial infarction, one of three heart diseases, published in the same issue of the journal Nature Medicine.

"What is clear now is that there are major disruptions in the gut microbiota of heart patients, and these changes may have begun many years before heart disease symptoms appeared and were diagnosed." These changes in the microbiome cannot be explained by drug therapy. Oluf Pedersen said.

The main limitation of these studies is that the investigators reported correlations rather than causal explanations for their observations. However, Professor Oluf Pedersen stressed that over the past decade, a large number of cellular and animal experiments have studied specific microbial microbiota-derived compounds – such as those identified in the current study – have demonstrated that an unbalanced gut microbiota may play a role in the development of heart disease.

"Interventions in humans and rodents have shown that at different stages of heart disease development, an unbalanced gut microbiome can be improved and partially restored by eating more plant-based and energy-controlled diets, avoiding smoking, and adhering to daily exercise." Professor Oluf Pedersen, who continues his research at Gentofte University Hospital, said: "It is time to translate the accumulated evidence on the role of the gut microbiome into more focused public health initiatives to try to prevent or delay morbidity and mortality associated with heart disease."

Reference Articles:

1. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nature Medicine, 2022

2.Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease. Nature Medicine, 2022