A striking new gut-brain link has been discovered by researchers at the Cleveland Clinic. The findings show how a metabolite produced by gut bacteria can amplify the severity of a stroke and impair a person’s recovery.
The research focused on a compound called TMAO (trimethylamine N-oxide), which is produced in the gut when certain microbes digest animal products such as red meat. Prior research has linked high blood levels of TMAO to heart disease and aging. While TMAO has been associated with increased stroke risk, this new research is the first to explore the links between gut bacteria and stroke, as mediated by TMAO production.
To confirm a link between TMAO and stroke severity the researchers first took fecal samples from two different human subjects, one with persistently high TMAO levels and the other with low levels. These fecal samples were then transplanted into microbe-free mouse models and the animals were subjected to an induced stroke. Stanley Hazen, a lead researcher on the project, says the difference in stroke severity between the two animal models was significant.
“Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity,” says Hazen.
Zooming in on the microbes responsible, the researchers found that an enzyme called CutC, produced by specific gut bacteria, played a critical role in the production of TMAO. When the gut bacteria gene that encodes for CutC was silenced the severity of stroke seen in the animals significantly dropped, affirming the role gut bacteria seemed to be playing in this process.
The researchers also explored whether this mechanism influences post-stroke recovery. Looking at short- and long-term outcomes in the animal models the new study found TMAO levels indeed worsened post-stroke functionality, and silencing CutC again improved those long-term outcomes.
Exactly how TMAO directly influences stroke severity is still unclear and the researchers suggest more work is needed to better understand these underlying mechanisms. Prior work from Hazen and colleague Weifei Zhu has pointed to links between enhanced blood clotting and TMAO.
Zhu says there is ongoing research exploring whether CutC gene silencing could be a way to either prevent stroke or help sufferers recover more rapidly. But in the short term the researchers say dietary interventions may be the best approach.
“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,” says Zhu. “Switching to plant-based protein sources helps to lower TMAO.”
The new study was published in the journal Cell Host & Microbe
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