A European-Israeli collaboration of researchers shows how severe abnormalities in the gut microbiota of patients with heart disease arise in two papers published in Nature Medicine.
Professor Oluf Pedersen of the University of Copenhagen, one of the senior lead researchers, calls for stronger and more focused public health initiatives to prevent or delay these common diseases, which are a leading cause of premature death worldwide, through a plant-based and energy-controlled diet, the avoidance of smoking, and daily exercise compliance.
The gut microbiome is a collection of billions of bacteria found in the human gut that can have both beneficial and negative effects on human health. They work as an inner chemical factory, producing a variety of molecules that support good health when they are in balance.
An unhealthy lifestyle, such as poor diet, smoking, lack of physical activity, or disease, can upset the balance, causing the microbiome to produce compounds that can cause a variety of non-communicable chronic disorders, such as myocardial infarction, angina, or heart failure, in people with a high genetic risk.
Scientists have already discovered that persons with chronic heart disease have changed gut microbiomes. They next discovered chemicals produced by the sick microbiome, such as trimethylamine (TMA), a bacterial molecule that induces arteriosclerosis after being modified in the human host’s liver.
These findings of a changed gut microbiome, however, are disputed because they were obtained in trials of treated patients. Patients with heart disease are given a variety of medications, each of which has the potential to alter the gut microbiome.
As a result, it was unclear medicines caused whether the disturbed gut microbiome of persons with cardiovascular problems or by the disease itself.
It is now clear that major disturbances occur in the gut microbiome of patients suffering from heart disease and that these alterations may start many years before onset of heart disease symptoms and diagnosis. These microbiome changes are not explained by drug treatments.
Professor Oluf Pedersen
Another difficulty is that heart disease frequently occurs in the early stages of obesity and type 2 diabetes, both of which are characterized by disturbed gut microbiomes. As a result, it’s still unclear if an unbalanced gut microbiome is a symptom of heart disease.
Heart diseases cause major disturbances in the gut microbiome
In 2012, a European collaboration of researchers created the EU-funded MetaCardis research project to examine the role of gut bacteria in cardiometabolic disease in order to answer these essential concerns.
Professor Oluf Pedersen of the University of Copenhagen is one of the consortium’s lead investigators, and he and his colleagues published the consortium’s findings in the journal Nature Medicine.
“We applied a study design that mirrors heart disease initiation and escalation over time, substituting for a longitudinal study of the gut microbiome that otherwise would be impossible to perform given the 50-60 years it takes to develop symptoms of arteriosclerosis and have the diagnosis of heart disease,” who carried out the research at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
Healthy persons, those with obesity and type 2 diabetes but no diagnosis of heart disease, and patients with myocardial infarction, angina pectoris, or heart failure were among the 1,241 middle-aged people recruited from Denmark, France, and Germany.
The researchers measured around 700 different bacterial species in the gut microbiome and evaluated their roles, then matched their findings to over 1,000 molecules circulating in blood, many of which came from the inner gut chemistry factory.
“We found that about half of these gut bacteria and blood compounds were modified by drug treatment and not directly related to heart disease or the early disease stages like diabetes or obesity occurring prior to diagnosis of heart disease,” says Professor Oluf Pedersen.
“Among the remaining half, about 75 percent of the disturbances of the gut microbiome occurred in the early disease stages of overweight and type 2 diabetes, many years before patients noticed any symptoms of heart disease.”
The early microbiome modifications, on the other hand, persisted in individuals with heart disease, who also had unique heart disease-related changes in the composition and function of the gut microbiome.
The diseased microbiome was characterized by a loss of bacterial cells and bacterial competencies at both the early dysmetabolic stage and the later stages of documented heart disease.
In addition, the patients’ gut flora were shifting away from producing health-promoting compounds like short-chain fatty acids and toward manufacturing hazardous compounds from the breakdown of certain dietary amino acids, choline, and L-carnitine. The imbalance of the gut microbiome was mirrored in blood compound analysis.
Plant-based and energy-controlled diets can help
The findings of gut microbiota and blood chemical abnormalities in patients with acute myocardial infarction, one of the three cardiac illnesses, were validated and extended in an Israeli study published in the same issue of Nature Medicine.
“It is now clear that major disturbances occur in the gut microbiome of patients suffering from heart disease and that these alterations may start many years before onset of heart disease symptoms and diagnosis. These microbiome changes are not explained by drug treatments,” says Oluf Pedersen.
The studies’ fundamental flaw is that the researchers present associations rather than causal explanations for their findings.
Professor Oluf Pedersen, on the other hand, emphasizes that a number of cellular and animal studies into specific microbiome-derived compounds, such as those identified in the current studies, have demonstrated how an imbalanced gut microbiome may play a role in the development of heart disease in the last decade.
“Intervention in both humans and rodents have shown that an imbalanced gut microbiome at various stages of heart disease development can be modified and partly restored by eating a more plant-based and energy-controlled diet, avoidance of smoking and compliance with daily exercise. It is time for translating the accumulated evidence of the role of the gut microbiome to more focused public health initiatives in attempts to prevent or delay morbidity and mortality related to heart disease,” says Professor Oluf Pedersen, who is continuing his research at Gentofte University Hospital.
