Baffling chronic pain eases after doses of gut microbes

What Rina Green calls her “living hell” began with an innocuous backache. By late 2022, two years later, pain flooded her entire body daily and could be so intense that she couldn’t get out of bed. Painkillers and physical therapy offered little relief. She began using a wheelchair.

Green has fibromyalgia, a mysterious condition with symptoms of widespread and chronic muscle pain and fatigue. No one knows why people get fibromyalgia, and it is difficult to treat. But eight months ago, Green received an experimental therapy: pills containing living micro-organisms of the kind that populate the healthy human gut. Her pain decreased substantially, and Green, who lives in Haifa, Israel, and is now 38, can go on walks — something she hadn’t done since her fibromyalgia diagnosis.

Green was one of 14 participants in a trial of microbial supplements for the condition. All but two reported an improvement in their symptoms. The trial is so small that “we should take the results with a grain of salt”, says co-organizer Amir Minerbi, a pain scientist at the Technion — Israel Institute of Technology in Haifa. “But it is encouraging [enough] to move forward.” The trial results and data from other experiments linking fibromyalgia to gut microbes are published today in Neuron¹.

Pain-inducing microbes

Fibromyalgia affects up to 4% of the global population and occurs in the absence of tissue damage. In 2019, Minerbi and his colleagues discovered that the gut microbiomes — the collection of microbes living in the intestines — of women with fibromyalgia differed significantly from those of healthy women². This led the scientists to wonder whether a dose of microbes from healthy people would ease the pain and fatigue caused by the condition. After all, previous research³ had shown that gut microbes might indirectly influence an array of chemical signals tied to pain perception.

How pain is misunderstood and ignored in women

The team transplanted minuscule samples of microbe-laden faeces from both women with fibromyalgia and healthy women into mice without any microbes in their bodies. The researchers found that mice that received microbes from women with fibromyalgia showed signs of greater sensitivity to pain in response to pressure, heat and cold than did mice that got microbes from healthy women. The first group also showed more evidence of spontaneous pain.

The team next transplanted faeces from healthy women into mice that had been colonized with fibromyalgia-associated microbes and then treated with antibiotics. These mice showed reduced symptoms of pain after the transplant. Mice that received both transplants but didn’t get antibiotics showed no improvement.

The researchers then conducted a trial with 14 women, including Green, who had severe, treatment-resistant fibromyalgia. All the participants received antibiotics and then, over ten weeks, regularly swallowed capsules containing gut bacteria from healthy women. Twelve reported improvement in symptoms such as pain, anxiety and sleep disturbances. Fatigue was a common side effect of the treatment.

The researchers note that gut microbes from people with fibromyalgia might prompt the immune system to attack neural circuits that are involved in pain. The microbes also metabolize compounds secreted by the human liver into molecules that can affect pain sensitivity.