- CCM disease, which occurs in one in 100 people, causes stroke and seizures
- Tests on mice showed certain gut bacteria triggered the formation of clusters that cause these seizures
- Looking at human models it seems the same is true for people
Gut bacteria could be the cause of a crippling hard-to-treat brain disease, a new study suggests.
Cerebral cavernous malformations (CCMs) are clusters of dilated, thin-walled blood vessels in the brain that can cause stroke and seizures.
According to new research published today, bacteria in the gut microbiome drive the formation of these clusters.
Currently there is not drug available to treat CCM. The only treatment option is surgical removal.
The study on cerebral cavernous malformations by researchers the University of Pennsylvania is part of a growing swell of research showing links between the gut and the brain (file image)
The study by researchers from the Perelman School of Medicine at the University of Pennsylvania is part of a growing swell of research showing links between the gut and the brain.
CCM disease, which occurs in about one in 100 to 200 people, can present in two forms.
One is sporadic, accounting for 80 percent of cases, and is most frequent in older individuals. The remaining 20 percent are familial, inherited cases.
In 2016, Dr Mark Kahn, a professor of Cardiovascular Medicine, discovered the molecular mechanism in cells that underlies CCM formation.
In the current study on mice, the team discovered that this molecular pathway is activated by TLR4, a receptor for certain bacteria.
Activation of this receptor vastly accelerated CCM formation, they found.
Conversely, if the scientists blocked this receptor using drugs, they prevented CCMs from forming.
Crucially, TLR4 primarily responds to bacteria in the gut.
Dr Alan Tang, a student in the Kahn lab, proposed that bacteria from the animal’s gut microbiome may drive CCM formation.
To test this theory, he examined CCM formation in mice that were housed under germ-free conditions or treated with antibiotics to reduce the number of bacteria living in the gut.
In both cases, CCM formation was dramatically reduced, demonstrating a key role for bacteria in the pathology of CCM disease.
They then looked at data on human CCM patients.
‘Some of these patients experience severe stroke by the age of two and others have no symptoms over their lifetime,’ Kahn said. ‘What makes the disease outcome so variable?’
They discovered that people with more TLR4 receptors tended to have a higher numbers of CCM lesions, suggesting that the issue identified in mice is also present in humans.
These studies identify an unexpected, direct link between the microbiome and a common cerebrovascular disease.
‘This suggests that treatments designed to block TLR4 signaling or alter the microbiome may be used to treat this disease,’ Dr Kahn said.