Gut Instinct: New discovery sheds light on brain disease
A UNM doctor’s expertise with a devastating inherited neurological condition that disproportionately affects New Mexico Hispanics contributed to a new study demonstrating the powerful effect intestinal bacteria can have on brain health.
The study, published online in the journal Nature on May 10, opens the door to potential treatments for the disease and adds to the growing understanding of how the gut microbiome affects the brain and immune system.
Leslie Morrison, MD, professor emerita in the departments of Neurology and Pediatrics in the UNM School of Medicine, and Blaine Hart, MD, professor in UNM’s Department of Radiology, were among 30 co-authors listed in the paper. The condition – cerebral cavernous malformation (CCM) – causes tangles of leaky capillaries in the brain called cavernous angiomas. Blood-swollen nodules can burst open, causing paralysis or death.
The Nature study, led by cardiologist Mark Kahn, MD, at the University of Pennsylvania, showed that eradicating bacteria in the guts of mice genetically engineered to develop cavernous angiomas prevented the brain lesions from developing.
“It was very surprising,” says Morrison, who studies a genetic defect predisposing Hispanic New Mexicans to develop a form of the disease linked to a gene mutation among early Spanish settlers. “It’s a new avenue for us to explore.”
Morrison and Hart’s efforts to identify the genes driving many CCM cases helped lay the groundwork for the discovery, said Richard S. Larson, MD, PhD, executive vice chancellor at the UNM Health Sciences Center. “I’m very proud UNM could play such a significant role in identifying the potential causes of this disease, which affects so many of our residents,” Larson says. “It’s a real tribute to the quality of the science we do here.”
The findings emerged from an accidental discovery by the UPenn team, which was investigating cerebral cavernous malformations in mice with a genetic defect similar to one that affects humans, Morrison adds.
Midway through the study, Kahn’s lab was moved into a new, sterile building. A graduate student noticed that mice that had been genetically engineered to develop cavernous angiomas failed to do so. Further investigation revealed that in their old environment the mice were infected with gut bacteria that released molecules that stimulated special receptors known as TLR4 in the cells lining the capillaries in the brain.
Signals from these TLR4 receptors in turn cause the cavernous angiomas. The scientists showed that when the mice were fed antibiotics – eliminating the gut bacteria – the blood vessel tangles failed to form. “It was really the serendipity of changing the lab that really sent them on this path,” Morrison says.
Now that the researchers have documented the neurological effect of gut bacteria in mice, they’re studying the same process in humans, she says. That entails collecting stool samples from people carrying the CCM gene so their gut bacteria can be examined.
“This has opened up a new door for exploration,” Morrison says. “We’re really hoping that this will increase people’s awareness and excitement about possible treatments in the future, but also spur them on to participating as much as possible in the research.”