Cleveland Clinic research identifies link between gut microbes, stroke

The gut microbiome impacts stroke severity and functional impairment following stroke, according to new findings from Cleveland Clinic researchers published in Cell Host & Microbe.

The research was led by Weifei Zhu, PhD, and Stanley Hazen, MD, PhD, of Cleveland Clinic's Lerner Research Institute. The study builds on more than a decade of research spearheaded by Hazen and his team related to the gut microbiome's role in cardiovascular health and disease, including the adverse effects of trimethylamine N-oxide (TMAO), a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.

Previously, the researchers discovered that elevated TMAO levels can lead to the development of cardiovascular disease. In clinical studies involving thousands of patients, they have shown that blood levels of TMAO predict future risk of heart attack, stroke, and death, findings that have been replicated around the world. Earlier studies, also led by Zhu and Hazen, were the first to show a link between TMAO and enhanced risk for blood clotting.

For the new study, researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following stroke. The researchers also found that dietary changes that alter TMAO levels, such as eating less red meat and eggs, impacted stroke severity.

"Functionality after a stroke, which occurs when blood flow to the brain is blocked, is a major concern for patients," said Hazen, co-section head of Preventive Cardiology & Cardiac Rehabilitation in Cleveland Clinic's Miller Heart, Vascular & Thoracic Institute, in a statement. "To understand if choline and TMAO affect post-stroke functionality, in addition to stroke severity, we compared performance on various tasks pre-stroke, and then both in the short- and long-term following stroke."

The researchers found that a gut microbe enzyme critical to TMAO production called CutC drove heightened stroke severity and worsened outcomes. According to Zhu, targeting this gut microbe enzyme may be a promising approach to prevent stroke.

"When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished," she said in a statement. "Ongoing research is exploring this treatment approach, as well as the potential for dietary interventions to help reduce TMAO levels and stroke risk, since both a Western diet and a diet rich in red meat are known to elevate TMAO levels. Switching to plant-based protein sources helps to lower TMAO."