The findings, published in Cell Host & Microbe, pave the way for new stroke treatments and prevention strategies.
Dr Stanley Hazen and his team have been studying the gut microbiome’s role in cardiovascular health and disease for more than a decade, including the negative effects of TMAO (trimethylamine N-oxide), a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.
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“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.
“Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity.”
Dr Hazen and his colleagues previously discovered that high TMAO levels can lead to cardiovascular disease. They have shown that blood levels of TMAO predict future risk of heart attack, stroke, and death in clinical studies involving thousands of patients – findings that have been replicated around the world.
Previous research led by Drs. Zhu and Hazen, were the first to show a link between TMAO and an increased risk of blood clotting were Zhu and Hazen.
“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 Dr Hazen.
The researchers compared brain damage in preclinical stroke models with and without TMAO. Those with higher TMAO levels had more extensive brain damage and motor and cognitive deficits after stroke. Changes in TMAO levels, such as reducing red meat and eggs, 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 Dr 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.”
The researchers discovered that a gut microbe enzyme called CutC, which is required for TMAO production, increased stroke severity and adverse outcomes.
Dr Zhu believes that targeting this gut microbe enzyme may be a promising strategy for stroke prevention.
“When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” she said.
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“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.”