Does Fibromyalgia Pain Start in the Gut?

A new study finds that gut microbiota from fibromyalgia patients can induce pain in mice. Could this lead to new treatment options?

May 01, 2025

[Image description: Illustration of the central portion of the human body with the gastrointestinal tract highlighted.]

I’ve long been fascinated by the gut microbiome. Although scientists can now genetically sequence microbes to capture a snapshot of what inhabits the gut, many of these microbes have never been successfully grown in the lab. As a result, the gut microbiome—and the complex interactions between microbes and between microbes and their human host—remains somewhat of a mystery.

Many devastating diseases have already been linked to disruptions in the gut microbiome. For example, patients treated with life-saving antibiotics for difficult infections sometimes experience an overgrowth of Clostridium difficile (“C. diff”) after the antibiotics wipe out their beneficial gut bacteria. A game-changing treatment, known as fecal microbiota transplantation (FMT), involves transplanting fecal material from healthy donors to restore a healthy microbial balance and dramatically reduce C. diff infections.

But how else might the gut microbiome affect our health? A new study, recently published in Neuron, reports exciting new findings linking the gut microbiome to fibromyalgia, a chronic pain condition.

Here, I break down the major takeaways from this new study. You can also read the full text at the link below:

Cai W, et al. The gut microbiota promotes pain in fibromyalgia. Neuron. 2025 Apr 18:S0896-6273(25)00252-1. doi: 10.1016/j.neuron.2025.03.032.

What is Fibromyalgia?

Fibromyalgia is a chronic condition that causes widespread pain, extreme fatigue, sleep problems, and difficulties with memory and thinking. What makes fibromyalgia different from other types of pain is that it isn’t caused by an obvious injury, illness, or nerve damage. Instead, it falls into a newer category called "nociplastic pain," where the brain and nervous system process pain signals differently. About 2-4% of people—mostly women—are affected by fibromyalgia. Despite how common it is, we still don’t fully understand what causes it, and targeted treatments are limited. Many people with fibromyalgia also deal with digestive issues and depression, which can make living with the disease even more challenging.

Research shows that people with fibromyalgia have differences in both their central nervous system and their immune systems. Recently, scientists have also discovered that the gut microbiome looks different in people with fibromyalgia compared to healthy individuals. Since the gut microbiome has been linked to pain in other conditions like irritable bowel syndrome and nerve pain, scientists are now exploring whether changes in gut bacteria might play a role in fibromyalgia symptoms too.

Study Methods and Results

Researchers in Canada, Israel, and Ireland worked together to investigate if the gut microbiota from women with fibromyalgia could cause pain symptoms in mice. To test this, they collected stool samples from women diagnosed with primary fibromylagia (without other medical conditions) and from healthy women. Then, they transplanted these fecal microbiome samples into germ-free female mice—mice that have no gut bacteria of their own.

[Note: Germ-free mice provide incredible opportunities for researchers to study how gut microbes from patients with different diseases affect health when replicated in the lab. If you’d like to learn more, check out this podcast episode I recorded a few years ago with an expert on the topic: Probiotics, Gut Health, and the Microbiome with Dr. Rheinallt Jones.]

After the transplants, the scientists tracked changes in the mice's pain sensitivity, gut health, immune system, and brain function over time. They also studied whether replacing the fibromyalgia-associated bacteria with healthy bacteria could reverse the pain symptoms.

Major Findings in Mice:

Gut microbiota from fibromyalgia patients caused pain: Mice that received gut bacteria from fibromyalgia patients developed increased sensitivity to mechanical, heat, and cold stimuli, as well as signs of spontaneous muscle pain.
Pain symptoms were long-lasting: The fibromyalgia microbiota triggered persistent pain that lasted for at least four months. Over time, these mice also showed signs of depression-like behavior.
Gut inflammation was not the cause: Despite the pain, there were no signs of gut inflammation, intestinal barrier damage, or major immune disruptions in the gut.
Changes in the immune system: Mice with fibromyalgia microbiota had increased levels of certain inflammatory immune cells in their blood and signs of activated immune cells (microglia) in their spinal cords, which contributed to the pain.
Increased nerve sensitivity: The sensory neurons that detect pain (in the dorsal root ganglia) were more easily activated in mice with fibromyalgia microbiota, suggesting heightened nerve sensitivity.
Altered metabolism: Mice transplanted with fibromyalgia microbiota had changes in brain and body metabolism, including altered amino acids and reduced bile acids—both of which have been linked to pain processes.
[EXCITING!] Pain could be reversed by restoring healthy gut bacteria: When the researchers replaced the fibromyalgia microbiota with healthy microbiota (after clearing the gut bacteria with antibiotics), the mice’s pain symptoms were significantly reduced or reversed.

The finding that the pain in mice was reversible after restoring a healthy microbiome is the most exciting to me. The researchers asked the next logical question—could fecal microbiota transplantation (FMT) reduce the pain of women with fibromylagia?

The researchers conducted an open-label pilot study in 14 women with fibromyalgia to test whether FMT from healthy female donors could improve symptoms. After clearing their gut microbiota with antibiotics, participants received five oral FMT doses over 10 weeks. Stool analyses confirmed successful engraftment of donor gut microbes, and patients were monitored for changes in symptoms and microbiome composition.

After receiving fecal microbiota from healthy donors, most women in the study experienced meaningful improvements in their fibromyalgia symptoms. Pain levels dropped significantly in 12 out of 14 participants, and many also reported better sleep, less fatigue, and improvements in mood and overall quality of life. Sensitivity to cold pain decreased, and there were positive shifts in the gut bacteria and blood chemistry linked to pain regulation. The treatment was generally safe, with only mild side effects like temporary fatigue and mild digestive discomfort. However, because this was a small, open-label study without a placebo group, larger controlled trials are needed to confirm these results.

The Takeaway

This study established proof of principle that transplanting gut microbiota from fibromyalgia patients into mice induced pain. Most excitingly, altering the gut microbiome through eliminating the fibromyalgia microbiota and using FMT with healthy donor fecal microbiota samples reduced pain in mice, and in a small pilot study, it also led to pain reduction in women with fibromylagia!

I am hopeful this is just the first step of many towards meaningful progress in the development and approval of new treatment options for those who suffer from fibromyalgia.

Yours in health, Dr. Quave