edited by L. Lock, reviewed by R. Egan
Summary diagram depicting the role of pentadecanoic acid in the modulation of hepatic cholesterol metabolism and atherosclerosis progression.
Credit: Nature (2026). DOI: 10.1038/s41586-026-11142-x
A common gut bacterium produces a molecule that slows cholesterol production in the liver. When researchers gave the molecule to mice prone to artery disease, the animals developed roughly half as much fatty plaque as untreated controls.
The molecule acts on the same enzyme targeted by statins, the widely used cholesterol-lowering drugs. That connection offers a concrete explanation for something harder to untangle: how bacteria living in the intestine might influence the health of arteries elsewhere in the body.
Researchers at institutions including Sun Yat-sen University and Shenzhen Bay Laboratory in China identified the substance as pentadecanoic acid. Their study, published in Nature, followed its effects from bacterial production to cholesterol clearance.
Following a bacterial clue
Observational studies over the past two decades have shown that the gut microbiota plays an important role in metabolic health, and disruptions can lead to common disorders including diabetes, liver disease and cardiovascular disease. More recent cause-and-effect studies are trying to pinpoint the molecular mechanisms that drive the development of these conditions.
Investigating this connection, the researchers began with existing gut microbiome data from people with and without atherosclerotic cardiovascular disease, in which fatty deposits accumulate in artery walls. Several bacterial species were more abundant in healthy people, with Bacteroides uniformis standing out.
Was the bacterium helping protect arteries, or is it simply more common in healthier people?
To find out, the researchers gave it to male mice genetically prone to atherosclerosis that were fed a high-fat diet. After 12 weeks, treated mice had less plaque in their aortas and lower blood levels of LDL, often called "bad" cholesterol. Heat-killed bacteria did not produce the same benefits.
The key appeared to be something the living microbes produced. The team separated substances released into the bacterial culture fluid, testing which one helped the laboratory-grown liver cells take up LDL. Repeatedly narrowing the mixture led them to pentadecanoic acid.
Given directly to mice three times a week for eight weeks, the fatty acid lowered cholesterol and reduced plaque buildup by about half.
Making less, taking in more
The next puzzle was to untangle how a fatty acid could help clear cholesterol from blood.
Experiments showed that pentadecanoic acid binds to and inhibits HMG-CoA reductase, an enzyme needed to make cholesterol. As cholesterol production fell, liver cells increased their supply of LDL receptors: proteins that capture cholesterol-carrying particles from the bloodstream.
The two effects worked together. The liver made less cholesterol and took in more from circulating blood.
The researchers tested that explanation by disabling LDL receptor production specifically in the mouse liver. Without those receptors, neither the bacterium nor the fatty acid provided its usual protection against plaque buildup.
Changing the bacterium supplied another check. Engineered strains that made less pentadecanoic acid still colonized the gut but offered substantially weaker protection. That finding helped connect the bacterial product to the arterial benefit.
Can the effect carry over to people?
Pentadecanoic acid is a saturated fatty acid found in foods such as dairy fat. The study strengthens the evidence that gut microbes also supply it, but showing a protective mechanism in mice does not establish a treatment for people.
Human findings offer reasons to investigate further, alongside reasons for caution. A small 2024 trial in women with fatty liver disease found that adding pentadecanoic acid to a Mediterranean-style dietary intervention further reduced LDL cholesterol. However, a 2026 analysis of two long-running studies found no association between higher blood levels of the molecule and a lower incidence of cardiovascular disease.
The molecule is already marketed as a heart-health supplement. Yet "the clinical evidence supporting a cardiovascular benefit remains limited," cardiovascular specialist Ben Chen of Australia's Monash Victorian Heart Institute told Nature's news team.
It should be noted that the new experiments used only male mice, and human diets and gut communities could change the response seen in the animal experiments. Co-author Xiangyu Mou also disclosed a pending patent covering the molecule's use against atherosclerosis.
Sharing an enzyme target with statins gives researchers a promising mechanism to pursue. Larger human trials would need to establish whether supplying the fatty acid—or encouraging gut bacteria to make more of it—could safely reduce the artery disease that causes heart attacks and strokes.
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