Your gut handles a whole lot more than lunch. (Photo by PeopleImages.com - Yuri A on Shutterstock)

In A Nutshell

• People with clogged arteries have significantly fewer beneficial, anti-inflammatory bacteria in their guts compared to healthy individuals

• Two protective bacterial species, Slackia isoflavoniconvertens and Faecalibacterium prausnitzii, were notably depleted in patients with coronary artery disease

• Machine learning models could identify heart disease patients with strong accuracy based solely on their gut bacterial patterns and predicted metabolites

• Different strains of the same bacterial species carry different genes and have opposite effects on cardiovascular health, suggesting personalized microbiome-based treatments may be possible

The trillions of bacteria living in our intestines might play a bigger role in heart disease than scientists previously thought. Researchers report differences between the gut microbes of people with clogged arteries and those with healthy hearts.

Scientists from South Korea’s Sungkyunkwan University compared gut bacteria samples from 14 people with coronary artery disease and 28 healthy adults. Instead of just counting which bacteria were present, they went deeper by analyzing the genes these microbes carry and what those genes actually do.

People with coronary artery disease had significantly fewer beneficial bacteria in their guts. Two species in particular stood out: Slackia isoflavoniconvertens and Faecalibacterium prausnitzii. Both produce compounds called short-chain fatty acids that help keep inflammation in check throughout the body.

At the same time, patients had more bacteria from a family called Lachnospiraceae. Some of these bacteria have been linked to a compound called TMAO, which earlier studies connected to heart disease risk. However, when the team looked at the specific genes that produce TMAO, they found no real difference between patients and healthy people.

The study, published in mSystems, suggests the relationship between these bacteria and heart disease is more complicated than a simple TMAO connection.

Gut Bacterial Activity Shifts in Heart Disease

Study authors examined what these gut microbes were actually doing by looking at their metabolic pathways, essentially the chemical processes they perform.

Patients with coronary artery disease had bacteria that were breaking down more amino acids like arginine. This matters because arginine helps produce nitric oxide, a molecule that keeps blood vessels relaxed and flexible. Without enough arginine, blood vessels may not function as well.

Patients’ gut bacteria also showed a greater ability to ferment simple sugars like lactose and xylose, indicating their microbial communities had shifted toward different types of food processing.

Using computer models, the team predicted which compounds these bacteria might be producing. One molecule called inosine appeared at higher levels in patients, though what it’s doing in the context of heart disease remains unclear. Two other compounds were lower in patients compared to healthy controls.

Patients with coronary artery disease showed far fewer beneficial bacteria in their guts. (Credit: Studio Romantic on Shutterstock)

Machine Learning Spots Disease Patterns

The research team tested whether gut bacteria patterns could help identify people with coronary artery disease. They fed their data into a machine learning model that achieved strong predictive performance, correctly classifying patients versus healthy individuals with an area under the curve of 0.89. For context, a perfect test would score 1.0, while random guessing would score 0.5.

The most important factors in making these predictions were the predicted metabolite inosine, another compound called alpha-muricholate, and the beneficial bacterium Faecalibacterium prausnitzii.

While promising, these findings need validation in larger, more diverse groups before they could become part ofroutine health screening.

Not All Gut Bacteria Strains Are Created Equal

The study revealed something that could reshape how we think aboutgut bacteria and health: different strains of the same bacterial species can have completely different effects.

Take Akkermansia muciniphila, a bacterium often considered beneficial. In healthy people, this bacterium carried genes that let it break down complex plant fibers. In patients with coronary artery disease, those same genes were missing.

The team found something particularly interesting in Faecalibacterium prausnitzii. In healthy people, this bacterium carried a gene called mtxB that may help it avoid producing compounds that eventually turn into TMAO. This could help explain why having more of this particular bacterium seems protective.

These strain-level differences matter because they show that simply having a bacterial species present isn’t enough. The specific version of that species and what it can do may be what really counts.

What This Means

The study included 42 Korean adults who underwent health screenings between 2014 and 2021. Doctors diagnosed coronary artery disease based on chest pain, reduced blood flow to the heart, or confirmed blockages of at least 50% in major arteries. The researchers carefully matched patients with healthy controls of similar age, sex, andbody weight to ensure fair comparisons.

While the findings are intriguing, several limitations exist. The small sample size and predominantly male participants mean the results may not apply to everyone. Because researchers only took snapshots at one point in time, they can’t say whether bacterial changes cause heart disease or result from it. The study also predicted what bacteria might be producing rather than measuring those compounds directly.

Still, the research adds to growing evidence that the gut-heart connection deserves serious attention. Restoring beneficial bacteria or modifying gut microbial activity could someday become part of heart disease prevention or treatment strategies.

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Paper Summary

Methodology

Researchers collected stool samples from 14 coronary artery disease patients and 28 healthy controls who were matched using statistical methods to ensure similar age, sex, and body mass index profiles. DNA was extracted and sequenced using shotgun metagenomics, which sequences all genetic material in the sample rather than targeting specific genes. The team used multiple computational tools to identify bacterial species, reconstruct metagenome-assembled genomes (MAGs), analyze metabolic pathways, and predict microbial metabolites. Statistical models compared bacterial abundance and metabolic functions between groups.

Results

Fifteen bacterial species showed different abundance levels between coronary artery disease patients and controls. Several Lachnospiraceae family members increased in patients, while beneficial bacteria like Faecalibacterium prausnitzii and Slackia isoflavoniconvertens decreased. Metabolic pathway analysis revealed enrichment of urea cycle and L-citrulline biosynthesis in patients, along with increased capacity for amino acid and simple carbohydrate degradation. Three predicted metabolites differed significantly: inosine increased while C18:0e MAG and alpha-muricholate decreased in coronary artery disease patients. Reconstructed MAGs from patients showed increased nitrogen fixation and sulfite reduction capabilities.

Limitations

The study included a relatively small sample size of 42 participants, with only three women, limiting generalizability across populations and sexes. The cross-sectional design prevents determining whether microbial changes cause coronary artery disease or result from it. Metagenomic sequencing reveals metabolic potential but not actual activity, so observed genetic capabilities may not reflect real-time microbial function. The study population consisted entirely of Korean adults, so findings may not apply to other ethnic groups with different diets and genetic backgrounds.

Funding and Disclosures

This research was supported by a National Research Foundation of Korea grant funded by the Korean Government (grant number RS-2023-NR077149). The authors declared no conflicts of interest.

Publication Details

Lee S, Raza S, Lee EJ, Chang Y, Ryu S, Kim HL, Kang SH, Kim HN. 2025. Metagenome-assembled genomes reveal microbial signatures and metabolic pathways linked to coronary artery disease. mSystems. Published online November 6, 2025. doi:10.1128/msystems.00954-25

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