Fecal transplant as painkiller? Gut microbiota and fibromyalgia part II

The bacteria living in our intestines, collectively known as the gut microbiota, may play a role in fibromyalgia, a chronic condition marked by widespread pain, fatigue, and often digestive or mood issues.

Scientists have found that the gut microbiota in people with fibromyalgia differs from that of healthy individuals, and are now investigating whether these differences could actually cause some of the symptoms.

Recently, a small pilot study has explored whether transplanting gut bacteria - yes, faeces transplant - from healthy women could ease symptoms in women suffering from severe fibromyalgia.

Fourteen women with long-standing fibromyalgia, who had not improved despite standard treatments, took part. Each participant had previously tried at least two recommended medications and followed general lifestyle advice, yet they still struggled with intense pain and exhaustion.

The intervention involved cleansing the gut with antibiotics and laxatives, followed by five rounds of encapsulated fecal microbiota transplant, given every two weeks.

These capsules were made from the stool of screened, healthy female donors. Out of 14 participants, 11 completed all five treatments, and all were followed up for analysis.

Microbial change and symptom relief
Before the transplants, the fibromyalgia patients' gut bacteria had a unique profile, distinct from that of the healthy donors.

In humans with fibromyalgia and mice with fibromyalgia microbiota (read part 1 for more about that study), researchers have found reduced levels of specific bile acids and lower numbers of bacteria that normally process these acids.

After treatment, stool samples showed that the patients’ microbiomes more closely resembled those of their respective donors, indicating that the transplanted bacteria had effectively colonized the gut. Importantly, this microbial shift remained stable at the last testing two months after the final transplant.

The treatment was generally well tolerated, with side effects mainly limited to mild stomach upset and fatigue.

Most of the participants reported clinically meaningful reductions in pain. Specifically, 12 out of 14 women experienced a drop of at least two points in pain scores just one week after the final transplant. That was a statistically significant change in pain levels.

In addition to reduced pain, patients also reported improvements in sleep, anxiety, depression, and physical quality of life. Measures of cold sensitivity improved, while heat sensitivity showed a possible trend toward improvement. Tests of the nervous system's ability to dampen pain remained unchanged.

Changes in the body´s metabolism after transplant
To explore how the transplanted bacteria might be helping, researchers analyzed the metabolic products in both the stool and blood of the patients before and after the treatment.

They found changes in many types of molecules, including amino acids, bile acids, short-chain fatty acids, and hormones.

A reduction in butyrate, a short-chain fatty acid involved in gut health and inflammation control, was seen in the stool.

Also in the stool, several neuroactive amino acids, such as tryptamine and tyramine, were increased. Amino acid pathway analysis revealed significantly increased fecal concentration of aspartate and proline., This change in amino acids in the stool was accompanied by decreased blood levels of other amino acids, lysine, and kynurenine.

In the blood, one primary bile acid increased, while several others showed a possible rise.

Some hormone levels in the blood, such as cortisone and progesterone-related molecules, dropped after treatment. At the same time, androgen-related compounds rose in the stool.

These changes suggest that the new gut bacteria influenced and changed hormone, amino acid, and neurotransmitter pathways in the body.

Such changes may, potentially profoundly, affect the body's metabolism and functions, including changes in the brain and spinal cord. Thereby affecting pain level and mood.

Gut-brain connections and future research
Many people with fibromyalgia also suffer from digestive problems like irritable bowel syndrome, further strengthening the connection between gut health and fibromyalgia.

No major changes were found in the gut lining. This suggests that the gut microbiota in fibromyalgia influences the body in more indirect ways. Possibly by changing how the immune system behaves or altering metabolites that affect nerves and the brain.

Researchers also considered whether environmental factors, like stress, diet, infections, or inflammation, could affect gut microbiota and symptoms. These triggers are well-known to influence gut bacteria and are often reported by people with fibromyalgia as making their symptoms worse. Therefore, it is compelling to speculate that the gut microbiota could mediate some of these environmental effects.

This pilot study showed promising results, especially reductions in pain and improvements in quality of life. The participants knew they were receiving the treatment, which can influence the outcome. Nevertheless, it could provide a direction to explore in the future.

The absence of gut damage, along with the limited immune response and unchanged visceral sensitivity, suggests that gut microbiota in fibromyalgia contributes to peripheral changes, such as peripheral immune response, metabolomic alterations, pain, and muscle hypersensitivity, rather than through gut barrier dysfunction or inflammation.

It adds to growing evidence that gut bacteria may influence not just digestion, but also pain, mood, and immune responses.

About the paper that inspired:

First Author: Weihua Cai, Israel
Published: Neuron, July 2025
Link to paper: https://www.cell.com/neuron/fulltext/S0896-6273(25)00252-1