New research suggests that gut bacteria may play a role in increasing the risk of heart disease. Scientists have reported that certain microbes in the human digestive system produce a molecule, imidazole propionate (ImP), which is associated with an increased risk of developing cardiovascular disease. This discovery could offer new strategies for diagnosing and managing heart health more effectively.
“When you think about atherosclerosis, usually people think cholesterol, and indeed cholesterol plays an extremely important role,” said Ina Nemet of the Cleveland Clinic Lerner Research Institute. However, high cholesterol and conventional risk factors don’t fully explain every case. Nemet, who was not involved in the new research, suggested that ImP could be among the hidden factors contributing to heart disease.
How Gut Bacteria Influence Heart Disease
The research, reported in Nature by an international team of scientists, revealed that ImP, produced by gut bacteria digesting the amino acid histidine, is associated with the early stages of atherosclerosis—the narrowing of arteries due to the buildup of fatty plaque. This condition underlies many cardiovascular diseases, leading to serious health outcomes like heart attacks.
Researchers analyzed blood vessel images from about 2,200 study participants to detect early signs of cardiovascular disease. After controlling for age and family history, the team reported that people with early signs of cardiovascular disease were significantly more likely to have higher levels of ImP compared to those without heart disease risks. Because atherosclerosis often progresses silently until it becomes severe, identifying early markers like ImP might improve detection and intervention.
The Mechanics Behind the Molecule
The team went further, conducting experiments with mice to uncover precisely how ImP exacerbates heart disease. They discovered that ImP attracts immune cells, promoting inflammation and contributing directly to plaque buildup within artery walls. Remarkably, this harmful effect is independent of cholesterol, the usual suspect in heart disease.
“This activity is all cholesterol independent,” Nemet said, pointing to ImP as a potentially crucial therapeutic target beyond traditional cholesterol-lowering treatments.
Further investigations revealed that ImP exerts its influence by binding to a receptor known as the imidazoline-1 receptor (I1R or nischarin), which is found on immune cells. By blocking the interaction between ImP and this receptor, the scientists successfully halted the progression of atherosclerosis in mice, even when exposed to conditions typically promoting plaque formation.
“Once you know the receptor and the mechanism,” Nemet said, “that really opens new venues for treatment.”
Expanding the Landscape of Heart Disease Management
This finding positions ImP alongside other microbial byproducts, such as trimethylamine N-oxide (TMAO), which have been previously linked to cardiovascular risk, as an important marker. Unlike TMAO, which emerges prominently after consuming meats and energy drinks, ImP appears broadly relevant, offering novel perspectives on gut-heart interactions.
The authors emphasize the urgent need for new biomarkers and therapeutic targets to address heart disease effectively. Current approaches predominantly focus on managing cholesterol levels with statins, leaving gaps in treatment strategies for individuals still at risk despite currently available care.
“Individuals at risk for early vascular disease often remain unidentified,” researchers wrote. “Identification of the strong association of ImP with active atherosclerosis and the contribution of the ImP–I1R axis to disease progression opens new avenues for improving the early diagnosis and personalized therapy of atherosclerosis.”
Optimism for Heart Health
While the complexity of cardiovascular disease remains daunting, uncovering ImP’s role offers a promising new avenue. This discovery could facilitate the early detection of heart risks, enhance preventive strategies and enable precise therapeutic interventions that target gut microbiota.
Ultimately, these insights empower researchers and clinicians with a potential new option to combat one of the world’s leading health threats, bringing us closer to better cardiovascular outcomes through innovative science.
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