Transplanting bacteria from the feces of healthy people into the guts of mice and patients with fibromyalgia successfully reduced pain levels, opening up a potentinal avenue for new microbe-derived drugs to treat the enigmatic chronic pain condition.
In a very small, open-label pilot study of 14 women with severe fibromyalgia, 12 patients saw their pain decrease by two or more points on a 10-point scale after taking five oral capsules of donor bacteria, one dose every two weeks.
The results were published in the journal Neuron on Thursday, April 24.
While encouraging, the clinical results are still preliminary, Arkady Khoutorsky, Ph.D., a neuroscientist at McGill University in Montreal and senior author of the study, told Fierce Biotech in an interview. “It's an open label, there is no good control group, and so on,” he pointed out.
Khoutorsky and fellow study author Amir Minerbi, M.D., are now running a randomized controlled trial of the technique that aims to recruit around 100 patients.
“It's been already running for a couple of years,” Khoutorsky said, and, while results aren’t expected for another year and a half, preliminary analyses suggest patients are responding similarly to the pilot study.
A 2019 study led by Minerbi showed that women with fibromyalgia had different gut microbiomes than people without the disease, suggesting bacteria in the body may be playing a role.
The goal of the new study, Khoutorsky said, was to prove that altered microbes in the gut can cause fibromyalgia pain, rather than the other way around. The team began by taking stool samples from patients with fibromyalgia and transplanting bacteria from them into mice; doing so caused the mice to become more sensitive to pain.
Replacing the pain-inducing microbes with bacteria from healthy volunteers brought the rodents’ pain sensitivity back to normal.
“Then we tried to just build on this mouse work and run it in people,” Khoutorsky said.
But while fecal bacteria transplants are looking promising so far, Khoutorsky has no intention of further developing the technique as a fibromyalgia treatment.
“We don't see ourselves treating people with the stool of other people,” Khoutorsky said, though the transplants are done using sterile capsules much like pills. Instead, he said, the team is using the current trial as a proof-of-concept and next wants to identify the key bacteria involved in reducing pain and unravel the mechanism behind the effect.
“The idea of moving forward is to try to kind of isolate either bacteria or metabolites or immune mechanisms and target one of them separately or in combination,” Khoutorsky said. This not only removes a potential "ick" factor but also ensures that the treatment given is a consistent dose and not at risk of contamination with unwanted microbes.
Fibromyalgia is a chronic pain condition that affects around 2% to 4% of the population, predominately women. In addition to muscle and joint pain, the disease can also cause fatigue and memory issues, and many patients develop depression or anxiety. Despite being common, the mechanism driving the disease has yet to be pinned down.
“It's really hard to diagnose,” Khoutorsky said, “and the treatment is symptomatic because we don't understand the origin of this, the underlying pathology.”
That’s not to say there aren’t strong ideas about what causes fibromyalgia. One way the microbiome may cause pain in fibromyalgia is through bile acids, Khoutorsky said, chemicals from the liver that are normally processed by bacteria in our guts. If the bacterial species that normally do this processing work are absent or low in number, levels of bile acids may drop, too.
“Bile acids are known to be analgesic, meaning that they decrease pain,” Khoutorsky explained. “So, if you have less of them, you have more pain.”
Momentum is building toward harnessing the microbiome to treat fibromyalgia and other chronic diseases. A trial of 45 patients with fibromyalgia in China published last year found a similar therapeutic effect of fecal transplants, and a paper published in the journal Science several weeks ago found that treatment with a bile acid slowed osteoporosis progression in mice and seems connected to better outcomes in human osteoporosis patients as well.