Dr. Weihua Cai
Work done at McGill University
Article citation
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. The gut microbiota promotes pain in fibromyalgia. Neuron. 2025 Jul 9;113(13):2161-2175.e13. doi: 10.1016/j.neuron.2025.03.032. Epub 2025 Apr 24. PMID: 40280127.
https://www.sciencedirect.com/science/article/pii/S0896627325002521?via%3Dihub
The gut microbiota contributes to pain in fibromyalgia
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. It is thought to result from an overall increased sensitivity to pain. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome was unknown. A new study by Weihua Cai, working in the laboratory of Arkady Khoutorsky at McGill University, shows that gut microbiota from women with fibromyalgia (FM) can cause chronic pain and related symptoms in mice. This study shows altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.
When microbiota from patients with fibromyalgia were transplanted into germ-free mice, the mice developed persistent mechanical, heat, cold, and muscle hypersensitivity, as well as spontaneous pain, without motor deficits. With longer follow-up, they also showed depression-like behaviour. The FM microbiota induced low-grade immune activation, mirroring fibromyalgia pathology in humans. Furthermore, the researchers revealed broad metabolic disruption, including reduced levels of specific bile acids. In mice already colonized with FM microbiota, replacing their microbiota with that of healthy controls after antibiotic “reset” fully reversed pain behaviours and partly restored skin innervation.
Finally, an open-label trial in women with severe, treatment-refractory FM showed that encapsulated microbiota from healthy donors successfully engrafted and was associated with reduced pain, improved global symptom burden, sleep, mood, and quality of life. Fibromyalgia lacks clear mechanisms and effective, mechanism-based treatments. This work is the first to demonstrate that gut microbiota alterations in FM are not only associated with, but can drive chronic widespread pain and related neuroimmune and metabolic changes.
The demonstration that healthy microbiota can reverse established pain in mice, together with encouraging clinical signals in patients, provides a strong rationale for randomized controlled trials of microbiota-based therapies in FM and possibly other pain syndromes.
More broadly, the study establishes a general framework to investigate the role of microbiota in human pain conditions and to identify microbial and metabolite mediators of chronic pain.
About Dr. Weihua Cai
Dr. Weihua Cai is a neuroscientist specializing in chronic pain and gut-brain interactions. She conducted this work as a postdoctoral fellow under the supervision of Dr. Arkady Khoutorsky at McGill University. Dr. Cai led the study from conception through execution, integrating findings across multiple approaches and coordinating efforts across teams.
Dr. Cai is currently transitioning to an independent research position at INCI in Strasbourg, where she will continue to explore microbiota-driven mechanisms of pain and brain function.
Sources of funding
This study was supported by the Weston Family Foundation, the Louise and Alan Edwards Foundation, the Canadian Institutes of Health Research, the Fonds de recherche du Québec – Santé (FRQS), and the Israel Ministry of Health Chief Scientist Grant for Pilot Studies.