The gut microbiota promotes pain in fibromyalgia
Weihua Cai, May Haddad, R. 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-Étienne Lorenzo, Volodya Hovhannisyan, David Ho-Tieng, Vibhu Kumar, Behrang Sharif, Bavanitha Thurairajah, Jonathan A. 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 González, Yoram Shir, Amir Minerbi, Arkady Khoutorsky
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.