Until now, cholesterol was considered the most important risk factor. However, Spanish researchers have discovered a new mechanism linked to intestinal bacteria.
There is increasing evidence of the crucial role that the gut microbiota plays in cardiovascular health. Now researchers from the Spanish National Center for Cardiovascular Research Carlos III (CNIC) have discovered that a molecule produced by bacteria in our intestines causes atherosclerosisa condition that can ultimately lead to a stroke and heart attack.
The discovery, published in Natureopens the door to the one hand detecting this molecule in the blood for early diagnosisand on the other hand, developing drugs that can neutralize it to prevent cardiovascular problems.
“This metabolite is produced exclusively by intestinal bacteria,” explains Annalaura MastrangeloCNIC researcher and first author of the study. “In this work, we found that its presence in the blood is associated with the development of active atherosclerosis in apparently healthy individuals,” she adds.
“In active atherosclerosis, fat plaques tend to rupture more easily, leading to clots that cause strokes and heart attacks.” David Sanchohead of the CNIC Immunobiology Laboratory and leader of the study, Gut told Microbiota for Health.
In experiments conducted with mice administered this molecule, the researchers noted that the animals developed plaques in their blood vessels and also showed increased systemic inflammationwhich also contributes to the development of atherosclerosis. “This is important because it opens a new therapeutic avenue,” says Sancho.
Gut metabolites and cardiovascular health
This isn’t the first time a molecule produced by gut bacteria has been linked to cardiovascular health. Some metabolites, such as Short-chain fatty acids: propionate, butyrate, acetate– it has been shown to have beneficial effectswhile others, like TMAO also contributes to atherosclerosis.
In this case, the CNIC scientists’ research stems from a project launched in 2017 that followed thousands of people Banco Santander employees between 40 and 55 years old —the PESA study— to find out when cardiovascular disease starts. They found that six in ten apparently healthy people already showed signs of atherosclerosis. Then Sancho and his team began to investigate what factors were behind this build-up of fatty plaques in the arteries. They noted that most people with active atherosclerosis had elevated levels of this bacterial molecule in their blood.
The Mediterranean diet, a potential protector
“Our work shows that lower levels of imidazole propionate are associated with better cardiovascular healthand that people who eat a diet rich in fruits, vegetables, whole grains, fish, tea and low-fat dairy products tend to have less of this metabolite in their blood“, explains Sancho. In contrast, they discovered that people who eat a Western diet, rich in fats, show increased levels of imidazole propionate.
For now, researchers remain cautious with dietary recommendations. Although the Mediterranean diet has been linked to lower levels of this metabolite and better cardiovascular health, Sancho notes that “it is currently unknown whether this molecule could have beneficial functions in other contexts, such as activating the immune system.”
The CNIC researchers also found that this molecule appears to promote atherosclerosis in mice, even when cholesterol levels are normal. This could explain why some apparently healthy people, without conventional risk factors such as high blood pressure or high cholesterol, can still develop cardiovascular disease.
A line of research with therapeutic potential
Then the scientists blocked the receptor for this molecule with drugs, they were able to prevent the onset of atherosclerosis and reduce its progression in mice– opening the door to the development of new treatments based on the relationship between gut bacteria and cardiovascular health.
Reference
Mastrangelo, A., Robles-Vera, I., Mañanes, D. et al. Imidazole propionate is a driver and therapeutic target in atherosclerosis. Nature (2025). https://doi.org/10.1038/s41586-025-09263-w
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