The population of bacteria in the gut, known as the microbiome, is of great interest to researchers hoping to harness it to treat a host of diseases. A team at Brigham and Women's Hospital has a unique approach to studying the microbiome and its relation to multiple sclerosis (MS)—one that could provide a completely new way to treat the neurological disorder, they believe.
The approach involves a microRNA in the microbiome that increases when MS peaks in mouse models of the disease. When the researchers made a synthetic version of the microRNA and gave it to the mice as an oral treatment, it suppressed symptoms of the disease. They published their findings in the journal Cell Host & Microbe.
The researchers studied the microbiome of the mouse models of MS and made a surprising discovery: When they took fecal matter from animals experiencing peak symptoms and transferred it to other mice, the animals receiving the material were protected from MS.
A closer examination of the microbiome showed that it was not the bacteria itself providing the protection, but rather a microRNA called miR-30d. The Brigham and Women’s team went on to show that miR-30d is abundant in samples from patients with relapsing-remitting MS.
So why would giving the troublesome microRNA back as a treatment work to suppress MS? The researchers set out to answer that question by studying which parts of the mouse microbiome changed when they received the synthetic miR-30d.
They discovered that the treatment caused the bacterial strain Akkermansia muciniphila to grow in the gut. That’s important, because Akkermansia muciniphila had previously been shown to have anti-inflammatory properties.
What’s more, immune cells known as regulatory T cells, or Tregs, grew in response to the microRNA. That also helped suppress MS symptoms, the researchers reported.
This is not the first time the gut microbiome has been credited with producing an anti-inflammatory response in MS. Earlier this year, researchers from the University of California, San Francisco and the University of Toronto demonstrated that microbes in the gut activate plasma cells, which in turn produce anti-inflammatory antibodies in the central nervous system.
Targeting the gut microbiome could prove useful in treating other brain diseases, like Parkinson’s. A team at the Johns Hopkins University School of Medicine found that the misfolded alpha-synuclein proteins that have been implicated in Parkinson’s can travel from the gut to the brain. They believe the discovery could inform new therapies for early intervention in the disease.
The Brigham and Women’s researchers recognize that treating MS with a microRNA from the gut that peaks along with symptoms may be counter-intuitive, but they believe further research into miR-30d could point to new ways for modulating the microbiome. The team, led by senior author Howard Weiner, M.D., who co-directs Brigham and Women’s Ann Romney Center for Neurologic Diseases, is now planning further studies to translate the findings into a therapy for people with MS and possibly other conditions marked by inflammation.
“Our findings, which show that a microRNA can be used to target and influence the microbiome with precision, may have applicability for MS and many other diseases, including diabetes, ALS, obesity and cancer," he said in a statement.