A new study suggests that bacteria in the gut may influence the structure of the brain’s blood vessels—and may be responsible for malformations that can lead to stroke and epilepsy. Published in Nature, the research adds to an emerging dialogue that connects disorders of the nervous system to intestinal microbes.
Funded by the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), the study investigated the mechanisms that cause cerebral cavernous malformations (CCMs) to form in in genetically-engineered mice. CCMs are clusters of dilated, thin-walled blood vessels that can lead to seizures or stroke when blood leaks into the surrounding brain tissue. At the end of the study scientists discovered an unexpected link to bacteria in the gut—when bacteria were eliminated, the number of lesions dramatically 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,” says Jim I. Koenig, Ph.D., program director at NINDS.
While investigating this link, Alan Tang noticed that the few mice with dramatic lesions had developed bacterial abscesses in their abdomens. The abscesses contained Gram-negative bacteria. The team found that Gram-negative bacteria produce molecules called lipopolysaccharides (LPS), which are activators of innate immune signaling.
Researchers found that by blocking TLR4, an LPS receptor, lesions were greatly reduced.
“These results are especially exciting because they show that we can take findings in the mouse and possibly apply them at the human patient population,” said Koenig. “The drug used to block TLR4 has already been tested in patients for other conditions, and it may show therapeutic potential in the treatment of CCMs, although considerable research still remains to be done.”
