New Cleveland Clinic Research Identifies Link Between Gut Microbes and an Elevated Risk for Abdominal Aortic Aneurysms

Cleveland Clinic researchers have discovered a connection between elevated blood levels of TMAO (trimethylamine N-oxide) — a byproduct of gut bacteria digestion of 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 life-threatening condition, including faster rates of aneurysm expansion and greater risk for needing surgery.

“These results suggest targeting TMAO levels may help prevent and treat aneurysmal disease beyond surgery,” said lead author Scott Cameron, M.D., section head of Vascular Medicine at Cleveland Clinic. “We currently have no therapies except surgery or percutaneous intervention to treat abdominal aortic aneurysms that are particularly effective, and we have no blood tests to predict who is going to have an aneurysm and who will do well. With one of the largest volumes of aortic cases in the United States, we hope we can apply these findings to help future patients.”

Abdominal aortic aneurysm is a bulge in the part of the aorta that runs through the abdomen. Normally, the aorta’s wall is strong enough to manage the constant pressure of blood pumped out by the heart. However, various factors like aging, smoking and other medical conditions can weaken it.

Abdominal aortic aneurysms affect millions of patients annually and can rupture with an increased risk as they enlarge. An aneurysm repair by either endovascular (performed inside the blood vessels) or open surgery is typically recommended for larger aneurysms.Abdominal aortic aneurysms usually have no symptoms until they rupture or are close to rupturing.

“TMAO is made by gut microbes, with levels being higher when eating animal products and red meat” said senior author Stanley Hazen, M.D., Ph.D., chair of Cleveland Clinic’s Cardiovascular and Metabolic Sciences Department and co-section head of Preventive Cardiology. “Medication targeting this pathway has been shown to block aneurysm development and rupture in preclinical models but are not yet available for humans.These results are important to share because they show how important diet may be in helping prevent or treat patients with aorta dilation or early aneurysm compared to current clinical practice, which is to monitor until surgery is needed.”

This study builds on more than a decade of research led by Dr. Hazen related to the gut microbiome’s role in cardiovascular health and disease, including adverse effects of TMAO. The research team has published numerous studies linking high TMAO levels to increased risk of developing both chronic kidney disease and cardiovascular disease, including adverse events like heart attack and stroke.

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 seminal discoveries related to the involvement of the gut microbiome including the TMAO pathway in cardiovascular and metabolic diseases have been replicated around the world. TMAO testing is now widely available and has been incorporated in clinical practice.

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