Published in Nature Medicine, the research suggests the existence of a specific microbiome signature that produces compounds able to trigger certain disorders in genetically susceptible people.
“We applied a study design that mirrors heart disease initiation and escalation over time,” explains principal investigator Professor Oluf Pedersen from the University of Copenhagen.
“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."
A European-wide consortium of researchers began recruiting 1,241 middle-aged individuals living in Denmark, France and Germany.
The sample included healthy individuals as well as individuals with obesity and type 2 diabetes but lacking a diagnosis of heart disease,
Other subjects included in the trial were those suffering from either myocardial infarction, angina pectoris or heart failure.
Obesity & diabetes
The investigators quantified about 700 different bacterial species and estimated their functions in the gut microbiome
These were then compared to findings taken from more than 1,000 compounds circulating in blood with many of these compounds originating from the inner gut environment.
“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,” Professor Pedersen comments.
“Among the remaining half, about 75% 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.”
Findings from this study were validated and extended in further research conducted in Israel that features in the same issue of Nature Medicine.
Here, the team performed a series of clinical and multi-omic profiling, including serum metabolomics and gut microbiome data, for 199 patients with acute coronary syndrome (ACS).
These patients were found to have distinct serum metabolome and gut microbial signatures and were depleted in a previously unknown bacterial species of the Clostridiaceae family.
"It is now clear that major disturbances occur in the gut microbiome of patients suffering from heart disease,” adds Professor Pedersen.
“These alterations may start many years before onset of heart disease symptoms and diagnosis. These microbiome changes are not explained by drug treatments."
Previous studies have highlighted the alterations of the gut microbiome in people with chronic heart disease.
Further investigations have identified compounds produced by the diseased microbiome, such as trimethylamine (TMA) that can undergo change in the liver and go on to play a role in atherosclerosis formation in humans.
However, these findings of altered gut microbiome are not conclusive given that the results were found in medicated patients.
The prescribed drugs can modify the gut microbiome and thus it was unclear whether drugs or heart disease itself that caused the disrupted gut microbiome in those with cardiovascular conditions.
Furthermore, heart disease often develops alongside the early stages of overweight and type 2 diabetes, also characterised by a disrupted gut microbiome.
The research team ask the question as to whether an imbalanced gut microbiome is a feature of heart disease itself.
Source: Nat Med
Published online: doi.org/10.1038/s41591-022-01688-4
“Microbiome and metabolome features of the cardiometabolic disease spectrum.”
Authors: Fromentin S et al.
Source: Nat Med
Published online: doi.org/10.1038/s41591-022-01686-6
“Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease.”
Authors: Talmor-Barkan, Y et al