- Experts are interested in how microorganisms in the gut impact heart health.
- A recent study has identified possible bacterial species associated with coronary artery disease, as well as critical metabolic pathways, metabolic products, genes, and functional differences of specific bacteria.
- This research could pave the way towards using gut-related strategies to address coronary artery disease.
According to the
Research is ongoing about the possible factors involved, including how the microorganisms in the gut may play a role.
A study recently published in mSystems examined stool samples from healthy controls and people with coronary artery disease and identified distinct differences.
The results found that the consideration of gut bacteria and their metabolites may help with identifying risk for coronary artery disease.
The findings also offer more insight into how gut bacteria may affect coronary artery disease, which could lead to cardiovascular disease treatments focusing on this relationship.
In the current study, researchers sought to examine the relationship between gut microorganisms, functional pathways, and coronary artery disease.
They selected participants from the Kangbuk Samsung Cohort Study. They excluded participants with certain risk factors, such as cancer history or recent use of antibiotics.
They chose 14 individuals with coronary artery disease and 28 controls, collecting fecal samples from each. Three participants were female, and the average age of the participants was of around 53.
Researchers used a technique called
Patrick Kee, MD, PhD, a cardiologist at Vital Heart & Vein, who was not involved in this study, explained more about the research methods to Medical News Today. Kee told us that:
“This approach [shotgun metagenomics] not only identifies which microbes are present but also reconstructs the metabolic potential of the microbial community — what biochemical pathways those microbes are capable of carrying out […] To make sense of the vast DNA data, the researchers used algorithms to group related fragments into complete or near-complete microbial genomes, known as metagenome-assembled genomes (MAGs).”
Researchers identified 520 bacterial species when looking at data from all participants. While bacterial diversity was similar for both groups, researchers did find 15 bacterial species where the amounts present were vastly different between the two groups.
Seven bacterial species were greatly increased in the coronary artery disease group, and eight species were depleted compared with Healthy controls.
The authors suggest that one of the shifts that might happen in people with coronary artery disease is an increase in some bacteria and fewer amounts of bacterial species that make
The data also found differences in several metabolic pathways between the two groups. Some pathways were enriched, while others were depleted.
The specific bacteria contributing to these pathways differed. There were also differences in amino acid and carbohydrate metabolism in the coronary artery disease group compared to controls.
Study author Han-Na Kim, PhD, Assistant Professor at Sungkyunkwan University (SAIHST) in Seoul, Republic of Korea, explained to MNT:
“What we found was not only a difference in which bacteria were present, but also in what biological functions they performed. People with [coronary artery disease] had markedly fewer protective microbes that produce short-chain fatty acids (SCFAs) — molecules that help reduce inflammation and support vascular health. In contrast, we observed higher activity in microbial metabolic pathways such as the urea cycle and L-citrulline biosynthesis, which are related to inflammation and cardiovascular stress. These functional changes suggest a shift from a balanced to a pro-inflammatory gut environment.”
Researchers also identified certain
One metabolite, inosine, was greatly increased among participants with coronary artery disease, while two others were significantly lower in this group.
Researchers sought to see if considering metabolites and bacterial taxa could help with identifying cases of coronary artery disease using a model called a random forest classification model.
Consideration of both factors appeared to be helpful. For the model considering bacterial species, Kim explained that “the microbial profile showed strong predictive performance […], indicating that gut microbiome data could contribute to a better understanding of cardiovascular risk when combined with established clinical measures.”
Using metagenome-assembled genomes, or MAGs, researchers identified bacterial species shared by participants with coronary artery disease and controls, as well as some only in the coronary artery disease group, and some only in the control group.
Certain metabolic functions were also higher for participants with coronary artery disease, while other metabolic functions were higher for the control group.
The study explains that the metabolic signatures in the coronary artery disease-derived MAGs were linked to cardiovascular problems and unusual changes in inflammatory gut bacteria (dysbiosis).
They further identified a number of important genes, which differed for the MAGs from the two groups, and even functional characteristic differences amongst the same types of bacteria.
“Through metagenome-assembled genome (MAG) analysis, we further found that bacteria of the same species can behave very differently depending on the host’s health condition,“ said Kim.
“Even microbes traditionally considered beneficial, such as Akkermansia or Faecalibacterium, showed strain-level differences: Some carried genetic traits related to inflammation or trimethylamine (TMA) production, a compound associated with atherosclerosis,” the researcher detailed.
This research does have limitations. Participants were already part of the Kangbuk Samsung Cohort Study, which could affect the available sample.
For example, this sample was all adults between the ages of 23 and 77. Since this study was cross-sectional, it cannot determine cause, and researchers highlight the need for long-term studies.
The researchers also acknowledged that while shotgun metagenomics helps show metabolic potential, it is still a limited approach, and future research could tackle a more direct angle.
Additionally, researchers only included a microbial species if at least 10% of the samples had it. Thus, rarer bacteria could be the subject of future research.
The study received funding via a grant from the Korean government, and the main paper did not specify the involvement of the study funders.
Kee also noted several limitations of the research, highlighting:
- “Small sample size and lack of ethnic diversity: 42 participants (mostly men and only 14 coronary artery disease subjects). The subjects were all Korean, who have different genetics, diets, and environmental factors, making it difficult to generalize the data from this ethnic group to other populations.
- Single timepoint design: Coronary artery disease develops over many decades, but the samples in this study were collected at a single time point and may not reflect the historical changes in the gut microbiota over the lifespan of the individuals.
- Lack of metabolomic validation: All functional inferences (pathway shifts, metabolite predictions) are based on DNA abundance; no metatranscriptomic or metabolomic validation was performed, so actual metabolic activity is unverified.
- The apparent favorable [predictive performance] must be viewed cautiously: This study is based on an incredibly small foundation, a cross-sectional study with only 42 subjects (with only 14 coronary artery disease patients), and the confidence intervals are wide (59–100%), indicating a high risk of overfitting.”
This study discusses factors that may impact coronary artery disease and, thus, potential areas to target when it comes to decreasing risk for cardiovascular disease.
Considering these tiny microorganisms could also make a difference in helping identify how high someone’s risk is for coronary artery disease.
Kim noted that:
“Although our study did not directly test clinical interventions, the microbial composition and functional pathways we identified were closely related to inflammation and metabolic stress, which are key mechanisms in cardiovascular disease […] Looking ahead, further research should evaluate whether monitoring or modulating the gut microbiome can improve early detection or risk stratification in heart disease.”
Kevin Shah, MD, a board-certified cardiologist and Program Director of Heart Failure Outreach at MemorialCare Heart & Vascular Institute at Long Beach Medical Center in Long Beach, CA, was also excited about future research in this area.
Shah told MNT that “the possibility of integrating gut-microbiome signatures into cardiovascular risk profiling is exciting for the future.“
“For now, our priority remains evidence-based interventions such as exercise and guideline-directed medical therapies, while the research community will further investigate microbiome-directed strategies in larger prospective trials,” he added.
