06.17.21
New findings from researchers at the Cleveland Clinic, published in Cell Host & Microbe, found that the differences across the human gut microbiome have significant associations with stroke severity, and functional impairment following a stroke, which may serve as a precedent for researching new potential interventions to help treat or prevent stroke.
The research, led by Weifei Zhu, PhD, and Stanley Hazen, MD, PhD of Cleveland Clinic’s Lerner Research Institute, builds on over ten years of research into correlations between the gut microbiome and cardiovascular health and disease. A major culprit of adverse effects in these studies was TMAO (trimethylane N-oxide), a byproduct of when gut bacteria digest certain nutrients abundant in red meat and other animal products.
“In this study we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models,” Hazen said. “Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity.”
In prior research, Dr. Hazen and his team discovered that elevated TMAO levels can lead to the development of cardiovascular disease based on clinical studies involving thousands of patients, each of which evidenced that TMAO is a predictor of future risk of heart attack, stroke, and death. Other studies have established a potential link between TMAO and enhanced risk for blood clotting.
“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,” Hazen said.
The researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with the higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following a 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,” Hazen, who is also co-section head of Preventive Cardiology and Cardiac Rehabilitation in Cleveland Clinic’s Miller Heart, Vascular, and Thoracic Institute, said.
“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 team found that a gut microbe enzyme critical to TMAO production, called CutC, drove heightened stroke severity and worsened outcomes.
“When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” Zhu said. “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.”
The research, led by Weifei Zhu, PhD, and Stanley Hazen, MD, PhD of Cleveland Clinic’s Lerner Research Institute, builds on over ten years of research into correlations between the gut microbiome and cardiovascular health and disease. A major culprit of adverse effects in these studies was TMAO (trimethylane N-oxide), a byproduct of when gut bacteria digest certain nutrients abundant in red meat and other animal products.
“In this study we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models,” Hazen said. “Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity.”
In prior research, Dr. Hazen and his team discovered that elevated TMAO levels can lead to the development of cardiovascular disease based on clinical studies involving thousands of patients, each of which evidenced that TMAO is a predictor of future risk of heart attack, stroke, and death. Other studies have established a potential link between TMAO and enhanced risk for blood clotting.
“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,” Hazen said.
The researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with the higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following a 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,” Hazen, who is also co-section head of Preventive Cardiology and Cardiac Rehabilitation in Cleveland Clinic’s Miller Heart, Vascular, and Thoracic Institute, said.
“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 team found that a gut microbe enzyme critical to TMAO production, called CutC, drove heightened stroke severity and worsened outcomes.
“When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” Zhu said. “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.”
