Researchers Connect Brain Blood Vessel Lesions to Intestinal Bacteria

A study in mice and humans suggests that bacteria in the gut can influence the structure of the brain’s blood vessels and may be responsible for producing malformations that can lead to stroke or epilepsy. The research, published in Nature, adds to an emerging picture that connects intestinal microbes and disorders of the nervous system. The study was funded by NINDS. 

Cerebral cavernous malformations (CCMs) are clusters of dilated, thin-walled blood vessels that can lead to seizures or stroke when blood leaks into the surrounding brain tissue. A team of scientists at the University of Pennsylvania investigated the mechanisms that cause CCM lesions to form in genetically engineered mice and discovered an unexpected link to bacteria in the gut. When bacteria were eliminated, the number of lesions was greatly diminished.

“This study is exciting because it shows that changes within the body can affect the progression of a disorder caused by a genetic mutation,” said Dr. Jim Koenig, program director at NINDS.

The researchers were studying a well-established mouse model that forms a significant number of CCMs following the injection of a drug to induce gene deletion. However, when the animals were relocated to a new facility, the frequency of lesion formation decreased to almost zero. 

“It was a complete mystery. Suddenly, our normally reliable mouse model was no longer forming the lesions that we expected,” said Dr. Mark L. Kahn, professor of medicine at Penn and senior author of the study. “What’s interesting is that this variability in lesion formation is also seen in humans, where patients with the same genetic mutation often have dramatically different disease courses.”