The gut microbiota promotes pain in fibromyalgia

Weihua Cai; May Haddad; Rana Haddad; Inbar Kesten; Tseela Hoffman; Reut Laan; Susan Westfall; Manon Defaye; Nasser S. Abdullah; Calvin Wong; Nicole Brown; Shannon Tansley; Kevin C. Lister; Mehdi Hooshmandi; Feng Wang; Louis Etienne Lorenzo; Volodya Hovhannisyan; David Ho-Tieng; Vibhu Kumar; Behrang Sharif; Bavanitha Thurairajah; Jonathan Fan; Tali Sahar; Charlotte Clayton; Neil Wu; Ji Zhang; Haggai Bar-Yoseph; Milena Pitashny; Emerson Krock; Jeffrey S. Mogil; Masha Prager-Khoutorsky; Philippe Séguéla; Christophe Altier; Irah L. King; Yves De Koninck; Nicholas J.B. Brereton; Emmanuel Gonzalez; Yoram Shir; Amir Minerbi; Arkady Khoutorsky

doi:10.1016/j.neuron.2025.03.032

The gut microbiota promotes pain in fibromyalgia

Weihua Cai, May Haddad, Rana Haddad, Inbar Kesten, Tseela Hoffman, Reut Laan, Susan Westfall, Manon Defaye, Nasser S. Abdullah, Calvin Wong, Nicole Brown, Shannon Tansley, Kevin C. Lister, Mehdi Hooshmandi, Feng Wang, Louis Etienne Lorenzo, Volodya Hovhannisyan, David Ho-Tieng, Vibhu Kumar, Behrang SharifBavanitha Thurairajah, Jonathan Fan, Tali Sahar, Charlotte Clayton, Neil Wu, Ji Zhang, Haggai Bar-Yoseph, Milena Pitashny, Emerson Krock, Jeffrey S. Mogil, Masha Prager-Khoutorsky, Philippe Séguéla, Christophe Altier, Irah L. King, Yves De Koninck, Nicholas J.B. Brereton, Emmanuel Gonzalez, Yoram Shir, Amir Minerbi, Arkady Khoutorsky

Research output: Contribution to journal › Article › peer-review

Abstract

Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.

Original language	English
Journal	Neuron
Early online date	18 Apr 2025
DOIs	https://doi.org/10.1016/j.neuron.2025.03.032
State	E-pub ahead of print - 18 Apr 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 The Author(s)

Keywords

bile acid
chronic pain
fecal microbiota transplantation
fibromyalgia
germ-free
immune system
inflammation
metabolism
microbiome
microglia

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/j.neuron.2025.03.032

Cite this

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., ... Khoutorsky, A. (2025). The gut microbiota promotes pain in fibromyalgia. Neuron. Advance online publication. https://doi.org/10.1016/j.neuron.2025.03.032

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title = "The gut microbiota promotes pain in fibromyalgia",

abstract = "Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.",

keywords = "bile acid, chronic pain, fecal microbiota transplantation, fibromyalgia, germ-free, immune system, inflammation, metabolism, microbiome, microglia",

author = "Weihua Cai and May Haddad and Rana Haddad and Inbar Kesten and Tseela Hoffman and Reut Laan and Susan Westfall and Manon Defaye and Abdullah, {Nasser S.} and Calvin Wong and Nicole Brown and Shannon Tansley and Lister, {Kevin C.} and Mehdi Hooshmandi and Feng Wang and Lorenzo, {Louis Etienne} and Volodya Hovhannisyan and David Ho-Tieng and Vibhu Kumar and Behrang Sharif and Bavanitha Thurairajah and Jonathan Fan and Tali Sahar and Charlotte Clayton and Neil Wu and Ji Zhang and Haggai Bar-Yoseph and Milena Pitashny and Emerson Krock and Mogil, {Jeffrey S.} and Masha Prager-Khoutorsky and Philippe S{\'e}gu{\'e}la and Christophe Altier and King, {Irah L.} and {De Koninck}, Yves and Brereton, {Nicholas J.B.} and Emmanuel Gonzalez and Yoram Shir and Amir Minerbi and Arkady Khoutorsky",

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year = "2025",

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day = "18",

doi = "10.1016/j.neuron.2025.03.032",

language = "English",

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Cai, W, Haddad, M, Haddad, R, Kesten, I, Hoffman, T, Laan, R, Westfall, S, Defaye, M, Abdullah, NS, Wong, C, Brown, N, Tansley, S, Lister, KC, Hooshmandi, M, Wang, F, Lorenzo, LE, 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, JS, Prager-Khoutorsky, M, Séguéla, P, Altier, C, King, IL, De Koninck, Y, Brereton, NJB, Gonzalez, E, Shir, Y, Minerbi, A & Khoutorsky, A 2025, 'The gut microbiota promotes pain in fibromyalgia', Neuron. https://doi.org/10.1016/j.neuron.2025.03.032

TY - JOUR

T1 - The gut microbiota promotes pain in fibromyalgia

AU - Cai, Weihua

AU - Haddad, May

AU - Haddad, Rana

AU - Kesten, Inbar

AU - Hoffman, Tseela

AU - Laan, Reut

AU - Westfall, Susan

AU - Defaye, Manon

AU - Abdullah, Nasser S.

AU - Wong, Calvin

AU - Brown, Nicole

AU - Tansley, Shannon

AU - Lister, Kevin C.

AU - Hooshmandi, Mehdi

AU - Wang, Feng

AU - Lorenzo, Louis Etienne

AU - Hovhannisyan, Volodya

AU - Ho-Tieng, David

AU - Kumar, Vibhu

AU - Sharif, Behrang

AU - Thurairajah, Bavanitha

AU - Fan, Jonathan

AU - Sahar, Tali

AU - Clayton, Charlotte

AU - Wu, Neil

AU - Zhang, Ji

AU - Bar-Yoseph, Haggai

AU - Pitashny, Milena

AU - Krock, Emerson

AU - Mogil, Jeffrey S.

AU - Prager-Khoutorsky, Masha

AU - Séguéla, Philippe

AU - Altier, Christophe

AU - King, Irah L.

AU - De Koninck, Yves

AU - Brereton, Nicholas J.B.

AU - Gonzalez, Emmanuel

AU - Shir, Yoram

AU - Minerbi, Amir

AU - Khoutorsky, Arkady

PY - 2025/4/18

Y1 - 2025/4/18

N2 - Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.

AB - Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.

KW - bile acid

KW - chronic pain

KW - fecal microbiota transplantation

KW - fibromyalgia

KW - germ-free

KW - immune system

KW - inflammation

KW - metabolism

KW - microbiome

KW - microglia

UR - http://www.scopus.com/inward/record.url?scp=105003646183&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2025.03.032

DO - 10.1016/j.neuron.2025.03.032

M3 - Article

C2 - 40280127

AN - SCOPUS:105003646183

SN - 0896-6273

JO - Neuron

JF - Neuron

ER -

The gut microbiota promotes pain in fibromyalgia

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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