The gut microbiota promotes pain in fibromyalgia
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Abstract
Abstract Fibromyalgia is a chronic syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. Despite affecting 2–4% of the population, primarily women 1 , the cause and underlying mechanisms of fibromyalgia remain elusive, and effective targeted treatments are currently unavailable. The gut microbiota of women with fibromyalgia differs from healthy controls 2,3 . However, it is unknown whether changes in gut microbiota have a causal role in mediating pain and other symptoms of fibromyalgia. Here, we show that fecal microbiota transplantation (FMT) from individuals with fibromyalgia, but not from healthy controls, into germ-free mice induces persistent pain hypersensitivity. FMT from fibromyalgia patients led to a reduction in intraepidermal nerve fiber density and alterations in the peripheral immune profile, and induced activation of spinal microglia, which contributed to the development of pain in mice. Notably, the pain hypersensitivity in mice that were administered microbiota from fibromyalgia patients resolved after FMT from healthy controls. Consistent with these findings, an open-label pilot study showed that transplanting microbiota from healthy individuals to humans with fibromyalgia alleviated pain and reduced overall symptom severity. Thus, altered gut microbiota has a causal role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.
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Fecal microbiota transplantation from fibromyalgia model mice into healthy recipients induced hyperalgesia in the recipient animals.
“Supporting a causal role, fecal microbiota transplantation from FMS model mice into healthy recipients induced hyperalgesia in the recipient animals (35).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [35]
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- Authors
- Cai, W., Haddad, M., Haddad, R., Kesten, I., Hoffman, T., Laan, R., Westfall, S., Defaye, M., Abdullah, N. S., Wong, C., Brown, N., Tansley, S., Lister, K. C., Hooshmandi, M., Wang, F., Lorenzo, L.-E., Hovhannisyan, V., Ho-Tieng, D., Kumar, V., Sharif, B., Thurairajah, B., Fan, J., Sahar, T., Clayton, C., Wu, N., Zhang, J., Bar-Yoseph, H., Pitashny, M., Krock, E., Mogil, J. S., Prager-Khoutorsky, M., Séguéla, P., Altier, C., King, I. L., De Koninck, Y., Brereton, N. J. B., Gonzalez, E., Shir, Y., Minerbi, A., & Khoutorsky, A.
- Affiliations
- McGill University (CA)
- Technion – Israel Institute of Technology (IL)
- Rambam Health Care Campus (IL)
- McGill University Health Centre (CA)
- University of Calgary (CA)
- Université Laval (CA)
- University College Dublin (IE)
- Corresponding author
- Shir, Yoram
- Minerbi, Amir
- Khoutorsky, Arkady
- ORCID
- Cai, Weihua
- Haddad, May
- Kesten, Inbar
- Westfall, Susan
- Defaye, Manon
- Wong, Calvin
- Tansley, Shannon
- Lister, Kevin C.
- Hooshmandi, Mehdi
- Wang, Feng
- Sharif, Behrang
- Clayton, Charlotte
- Wu, Neil
- Zhang, Ji
- Pitashny, Milena
- Krock, Emerson
- Mogil, Jeffrey S.
- Séguéla, Philippe
- Altier, Christophe
- King, Irah L.
- Brereton, Nicholas J.B.
- Shir, Yoram
- Minerbi, Amir
- Khoutorsky, Arkady
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2025-07
- Volume
- 113
- Issue
- 13
- Pages
- 2161-2175.e13
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W4409737152
- Cited by
- 59
- References
- 18
- Citations by year
- 2026: 29 · 2025: 25 · 2024: 5
- FWCI
- 36.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Louise and Alan Edwards Foundation
- Weston Family Foundation
- Santé
- Office of the Chief Scientist, Ministry of Health
- Canadian Institutes of Health Research (PJT-191992)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- fibromyalgia, gut microbiota, fecal microbiota transplantation, chronic pain, germ-free mice, immune activation, microbiota-targeted therapy, quality of life
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Adult, Animals, Female, Fibromyalgia, Humans, Mice, Inbred C57BL, Middle Aged, Pain, Quality of Life, Mice, Chronic Pain
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