This gut microbe may raise heart disease risk by hijacking cholesterol

If you have ever been told your cholesterol numbers look fine while a family history of heart disease still worries you, a new genetics study points to a place doctors rarely look: your gut. Researchers used a method called Mendelian randomization (a way of using inherited genetic variation to test cause and effect, similar in logic to a randomized trial) to ask whether specific gut bacteria might be nudging cholesterol levels toward higher heart disease risk. The result, published in the journal Medicine, points to one little-known microbe with an outsized connection to the arteries.

Key takeaways

• A Mendelian randomization study genetically linked a gut bacterium called GCA-900066755 to higher risk of coronary atherosclerosis (plaque buildup in the heart's arteries).
• The bacterium's effect runs partly through cholesterol: it tracks with higher LDL cholesterol and lower medium-HDL cholesterol, together explaining roughly 10 to 12 percent of its total link to heart disease risk.
• The finding contradicts other research suggesting this same bacterium may be beneficial in different contexts, so its overall role in the body is not settled.
• This is a genetic association study, not a clinical trial. No probiotic or supplement has been shown to change heart disease risk through this pathway.

Gut bacterium GCA-900066755 linked to heart disease risk

Researchers combed through genetic data on 473 gut microbiota traits and compared it against genetic data on coronary atherosclerosis (CA), the narrowing of heart arteries by fatty plaque, in 456,348 people of European ancestry. Using bidirectional Mendelian randomization, they identified 19 bacterial groups whose genetic signatures tracked with CA risk, 11 that appeared protective and 8 that appeared to raise risk.

One bacterium stood out: GCA-900066755. Its genetic signature was associated with a 16 percent higher relative odds of coronary atherosclerosis (odds ratio 1.16). That is not a measurement of an individual's real-world risk, but a signal, drawn from population genetics, that higher genetically predicted abundance of this microbe lines up with higher rates of the disease. When the researchers ran the analysis in reverse, they found no evidence that having CA changes how much of this bacterium a person carries, which supports the idea that the arrow of causation points from gut to heart rather than the other way around.

Coronary artery disease and cholesterol: who this affects

Coronary atherosclerosis is one of the leading drivers of heart attacks and cardiovascular death worldwide, and cholesterol has long been its best-known modifiable risk factor. This study adds a new wrinkle to that story: the type of cholesterol matters, and gut bacteria may help decide which type accumulates.

The researchers found that GCA-900066755 was negatively correlated with cholesterol carried in medium-sized high-density lipoprotein (HDL, often called "good" cholesterol), a pattern that would tend to lower CA risk. But the same bacterium was positively correlated with cholesterol carried in low-density lipoprotein (LDL, the "bad" cholesterol) across large, medium, and small LDL particles, all of which raise CA risk. In other words, more of this microbe appears to shift the cholesterol balance in the wrong direction, even though LDL subfractions themselves remain an area of active research as a cardiovascular risk marker. Anyone managing cholesterol, whether through diet, exercise, or medication, is the intended audience for why this matters: it suggests a microbial layer sitting underneath the numbers on a standard lipid panel.

Two-sample Mendelian randomization design behind the claim

The study leaned entirely on existing genome-wide association study (GWAS) data rather than recruiting new patients. Gut microbiota genetics came from a comprehensive microbiome GWAS covering 473 traits; cholesterol transport and distribution data came from large-scale metabolic biomarker studies covering 61 lipoprotein-related traits; and the coronary atherosclerosis data came from a GWAS catalog entry covering 16,041 CA cases and 440,307 controls, all of European ancestry.

Mendelian randomization works by using genetic variants as stand-ins for an exposure, the same logic that makes randomized trials useful, because the genetic variants a person inherits are assigned essentially at random and are fixed before disease develops. That design helps sidestep two of the biggest problems in ordinary microbiome research: reverse causation (does the disease change the microbiome, or does the microbiome change the disease?) and confounding from diet, medication, or lifestyle. The team then used a two-step mediation analysis to estimate how much of GCA-900066755's effect on CA passes through cholesterol traits specifically, arriving at the 10 to 12 percent figure highlighted above.

What this could mean for your cholesterol and gut health

For now, this is not a reason to buy a specific probiotic or microbiome test. GCA-900066755 is not a bacterium available as a supplement, and no product has been tested for its effect on this pathway. The practical takeaway is narrower: LDL and HDL cholesterol, the numbers a standard blood panel already measures, remain the most direct and actionable lever for lowering coronary atherosclerosis risk, and this study reinforces why doctors watch both the total number and which type of lipoprotein is carrying it.

If you already have elevated LDL cholesterol or a family history of coronary artery disease, the honest takeaway is that gut biology may be one more contributor worth discussing with a doctor as microbiome-informed medicine matures, not a reason to change behavior based on this study alone.

A contradiction the researchers cannot yet explain

The study's authors flagged an inconsistency worth taking seriously. Other experimental research has linked lower levels of GCA-900066755 to gastrointestinal disease (its abundance was reduced in patients with gallstones), and a separate study found that a seaweed-derived compound that increased levels of this same bacterium in mice was associated with lipid-lowering effects, not lipid-worsening ones. That is the opposite direction from what this Mendelian randomization study found for coronary atherosclerosis risk in humans.

The authors themselves note this contradiction rather than smoothing it over, concluding that GCA-900066755 may behave differently depending on context, health status, or which cholesterol pathway is engaged. Other limitations apply too: the analysis was restricted to people of European ancestry, so it is unclear whether the same pattern holds in other populations, and because the study relied on summary-level genetic data, the researchers could not break results down by age or sex.

What comes next for microbiome-based heart therapies

The authors call for two follow-up steps: experimental studies that manipulate GCA-900066755 directly to see whether changing its abundance actually changes cholesterol handling and CA risk, and replication of the genetic findings in non-European populations to check whether the association holds up across different genetic backgrounds. Until then, this remains a hypothesis-generating genetic signal rather than a proven mechanism.

Common Questions

What is Mendelian randomization? It is a research method that uses naturally inherited genetic variants as stand-ins for an exposure (like carrying more of a certain gut bacterium), which helps researchers infer cause and effect from genetic data without needing a traditional clinical trial.

What is GCA-900066755? It is a genus-level gut bacterium identified through microbiome genetic studies. It is not something currently tested for in a standard doctor's visit, and relatively little is known about its normal biological role.

Does this mean a specific probiotic can lower heart disease risk? No. This study did not test any probiotic, supplement, or intervention. It is a genetic association analysis, and no product has been shown to reduce coronary atherosclerosis risk through this pathway.

How much of the heart disease risk does cholesterol actually explain? The mediation analysis suggests cholesterol-related traits account for roughly 10 to 12 percent of this bacterium's total statistical link to coronary atherosclerosis risk. The remaining majority of the association works through pathways this study did not identify.

References

1. Xiaobo Liu, Kailin Shen, Fangtao Zhu, Cunwei Cheng, Haibin Yu (2026). Exploring the role of gut microbiota in coronary atherosclerosis through lipoprotein-mediated cholesterol transport and distribution. Medicine. https://doi.org/10.1097/md.0000000000050447
2. Healthy gut, healthy heart – Harvard Health. health.harvard.edu. https://www.health.harvard.edu/staying-healthy/healthy-gut-healthy-heart
3. Catherine E Lovegrove, Sarah A Howles, Dominic Furniss, Michael V Holmes (2024). Causal inference in health and disease: a review of the principles and applications of Mendelian randomization. Journal of Bone and Mineral Research. https://doi.org/10.1093/jbmr/zjae136