Research has indicated that there is a connection between gut microbes and heart health. Now scientists are revealing some of the details of that connection. For the first time, scientists have found evidence that the severity of a stroke and the prognosis after one occurs are both affected by gut bacteria. Knowing more about this connection can help improve outcomes for patients and may help prevent strokes from happening. The work has been reported in Cell Host & Microbe.
For more than a decade, researchers led by Stanley Hazen, M.D., Ph.D., of Cleveland Clinic's Lerner Research Institute have been investigating how gut microbes influence cardiovascular health and disease, and specifically, the role of a molecule called TMAO (trimethylamine N-oxide). TMAO is generated by gut bacteria when they break down molecules that are found in animal products and red meat.
"In this study, we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models," said Dr. Hazen, chair of the Department of Cardiovascular & Metabolic Sciences and director of Cleveland Clinic's Center for Microbiome & Human Health. "Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity."
Previous work by this team has suggested that high levels of TMAO can increase the risk of cardiovascular disease, and that TMAO is linked to a higher likelihood of blood clots. Patient studies by several groups have indicated that when people have high levels of TMAO, they are at greater risk of adverse heart events like heart attack, stroke, or death.
"This new study expands on these findings, and for the first time provides proof that gut microbes in general - and through TMAO specifically - can directly impact stroke severity or post-stroke functional impairment," said Hazen.
When the researchers assessed brain damage and TMAO levels in preclinical stroke models, they found that higher TMAO levels were connected to more extensive brain damage. Higher TMAO levels over time were also indicative of more motor and cognitive functional deficits after a stroke. Dietary changes that change TMAO levels, like reducing red meat and egg intake, also 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. "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."
An enzyme produced by gut microbes, called CutC, is known to be crucial to the production of TMAO. CutC was found to be a driver of stroke severity and caused worse outcomes. It may be possible to prevent strokes by targeting this enzyme, suggested study leader Weifei Zhu, Ph.D.
"When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished," said Zhu. "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."