Cleveland Clinic identifies a link between gut microbes and a higher risk of abdominal aortic aneurysms

• The results could lead to better monitoring and to new therapies or interventions designed to prevent ruptures.

Cleveland. Cleveland Clinic researchers have discovered a connection between elevated blood levels of TMAO (trimethylamine N-oxide), a byproduct of gut bacteria digesting nutrients found in red meat and other animal products, and a higher risk of abdominal aortic aneurysms.

The findings, published today in JAMA Cardiology, suggest that TMAO may play a role in the development, progression and severity of this potentially fatal condition, including faster aneurysm expansion and a higher risk of needing surgery.

“These results suggest that controlling TMAO levels could help prevent and treat aneurysmal disease beyond surgery,” said lead author Scott Cameron, M.D., head of the Section of Vascular Medicine at Cleveland Clinic. “We currently have no effective therapies other than surgery or percutaneous intervention to treat abdominal aortic aneurysms, nor blood tests that predict who will develop an aneurysm and who will do better. With one of the largest aortic case volumes in the United States, we hope to apply these findings for the benefit of future patients.”

An abdominal aortic aneurysm is a bulge in the part of the aorta that runs through the abdomen. Normally, the wall of the aorta is strong enough to withstand the constant pressure of blood pumped by the heart. However, factors such as age, smoking and certain diseases can weaken it.

Every year, millions of patients are affected by abdominal aortic aneurysms, which are more likely to rupture as they grow larger. For large aneurysms, repair is usually recommended, either through open surgery or endovascular surgery (inside the blood vessels). These aneurysms generally cause no symptoms until they are about to rupture or do rupture.

“TMAO is produced by gut microbes, and its levels are higher when people eat animal products and red meat,” explained Dr. Stanley Hazen, senior author, chair of Cleveland Clinic’s Department of Cardiovascular and Metabolic Sciences and co-section head of Preventive Cardiology. “Drugs that target this pathway have been shown to block aneurysm development and rupture in preclinical models, but they are not yet available for humans. These results are important to share because they show how relevant diet can be in helping to prevent or treat patients with a dilated aorta or early aneurysm, compared with current clinical practice, which is to monitor until surgery is needed.”

This study adds to more than a decade of research led by Dr. Hazen on the role of the gut microbiome in cardiovascular health and disease, including the adverse effects of TMAO. The research team has published numerous studies linking elevated TMAO levels to a higher risk of chronic kidney disease and cardiovascular disease, including events such as heart attacks and strokes.

Dr. Hazen also directs Cleveland Clinic’s Center for Microbiome and Human Health and holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis. His pioneering discoveries on the involvement of the gut microbiome, including the TMAO pathway, in cardiovascular and metabolic diseases have been replicated around the world. Today, TMAO testing is widely available and has been incorporated into clinical practice.

Disclosures: Dr. Hazen is named as co-inventor on pending and issued patents owned by Cleveland Clinic relating to the gut microbiome, cardiovascular diagnostics and therapeutics.

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical centre that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based on the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 81,000 employees worldwide are more than 5,743 salaried physicians and researchers, and 20,160 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,690-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, more than 276 outpatient facilities and locations in southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2023, there were 13.7 million outpatient visits, 323,000 hospital admissions and observations, and 301,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 132 countries.