In two papers in Nature Medicine, a European-Israeli research team shows how major disruptions occur in the gut microbiome of patients with heart disease. Given these latest insights from microbiome research, one of the lead researchers, Professor Oluf Pedersen from the University of Copenhagen, calls for stronger and more targeted public health initiatives to prevent or prevent these widespread diseases, which are one of the leading causes of premature death worldwide to delay plant-based and energy-controlled diets, cessation of smoking and adherence to daily exercise.
The human gut contains trillions of bacteria, collectively referred to as the gut microbiome, which can have both positive and negative effects on human health. When in balance, they act as an internal chemical plant, producing numerous health-promoting compounds. However, an unhealthy lifestyle – poor diet, smoking, lack of exercise or disease – can upset the balance and cause the microbiome to instead produce compounds that can trigger several non-communicable chronic diseases in people at high genetic risk, including myocardial disease heart attack, angina pectoris or heart failure.
Scientists have already discovered that the gut microbiome is altered in people with chronic heart disease. They then identified compounds produced by the diseased microbiome, such as a bacterial compound called trimethylamine (TMA), which causes atherosclerosis after modification in the human host’s liver.
However, these findings about an altered gut microbiome are questioned because they were obtained in studies with treated patients. Patients with heart disease receive various drugs that are known to alter the gut microbiome. As a result, it was unclear whether medications or heart disease itself caused the disrupted gut microbiome of people with cardiovascular disease.
Another complication lies in the fact that heart disease often develops along with the early stages of obesity and type 2 diabetes, which are also characterized by disrupted gut microbiomes. As a result, it has yet to be shown whether an imbalanced gut microbiome is a feature of heart disease itself.
Heart disease causes major disruptions in the gut microbiome
To answer these critical questions, a European consortium of researchers launched the EU-funded MetaCardis research project in 2012 to study the role of gut microbes in cardiometabolic diseases. Lead researchers include Professor Oluf Pedersen from the University of Copenhagen, who along with his colleagues published the consortium’s findings in the journal Nature Medicine.
“We applied a study design that reflects the onset and escalation of heart disease over time, replacing a longitudinal study of the gut microbiome, which would otherwise be inappropriate given the 50-60 years it takes for atherosclerosis symptoms to develop and diagnosis to be made impossible would be heart disease”, who conducted the research at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
Researchers recruited 1,241 middle-aged subjects from Denmark, France and Germany, including healthy subjects, subjects with obesity and type 2 diabetes who had no diagnosis of heart disease, and patients with myocardial infarction, angina or heart failure. The researchers quantified about 700 different types of bacteria and estimated their functions in the gut microbiome and compared these results to more than 1,000 compounds circulating in the blood, with many of these compounds originating from the inner gut chemical factory.
“We found that about half of these gut bacteria and blood connections were altered by drug treatment and are not directly related to heart disease or the early stages of disease, such as diabetes or obesity, that occur before heart disease is diagnosed,” says Professor Oluf Pedersen.
“In the remaining half, about 75 percent of gut microbiome disorders occurred in the early stages of obesity and type 2 diabetes, many years before patients noticed symptoms of heart disease.”
However, the early microbiome changes persisted in patients with heart disease, who additionally showed specific heart disease-related changes in the composition and function of the gut microbiome. Both in the early dysmetabolic stage and in the later stage of a diagnosed heart disease, the diseased microbiome was characterized by a loss of bacterial cells and bacterial competencies. In addition, patients showed a shift toward fewer types of bacteria known to produce health-promoting compounds, such as short-chain fatty acids, and more bacterial types that produce unhealthy compounds from the metabolism of certain amino acids, choline and L-carnitine. Analyzes of blood components reflected the imbalance of the gut microbiome.
Plant-based and energy-controlled diets can help
Findings on changes in gut microbiome and blood composition in patients with one of three heart conditions, acute myocardial infarction, were validated and extended in a study from Israel reported in the same issue of Nature Medicine.
“It is now clear that major disruptions occur in the gut microbiome of patients with heart disease and that these changes can begin many years before the onset of heart disease symptoms and diagnoses. These microbiome changes cannot be explained by drug treatments,” says Oluf Pedersen.
The primary limitation of the studies is that the researchers report associations rather than causal explanations for their observations. However, Professor Oluf Pedersen emphasizes that over the past decade, a number of cell and animal experiments using specific microbiome-derived compounds – such as those identified in the present studies – have shown how the imbalanced gut microbiome may play a role in the development of heart disease .
“Interventions in both humans and rodents have shown that an imbalanced gut microbiome at various stages of heart disease development can be modified and partially restored by eating a more plant-based and energy-controlled diet, avoiding smoking, and maintaining daily exercise It.” It is time to translate the accumulated evidence on the role of the gut microbiome into more targeted public health initiatives to prevent or delay morbidity and mortality associated with heart disease,” says Professor Oluf Pedersen, who conducts his research at Gentofte University hospital continues.