97: Human Antibody Responses to Gut Bacteria in Fibromyalgia

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Neuroimmunology, , ,

Background and Aims: Fibromyalgia (FM) patients exhibit distinct gut microbiome alterations, with specific bacterial taxa correlating with pain severity. Additionally, the transfer of FM IgG into mice triggered the transfer of FM symptoms. Previously identified a role for IgG autoantibodies in FM pain. Normally a portion of gut bacteria is coated by IgA, but IgG coating of gut bacteria is rare and often signals an abnormal immune response4. It remains unclear how microbiome community changes could drive the production of painful autoantibodies in FM. Here, we investigate whether specific gut bacterial taxa exhibited altered antibody coating in FM patients compared to pain-free controls.

Methods: Fecal samples were collected from FM patients and controls, flash-frozen, and bacteria were extracted for analysis. Using bacterial flow cytometry, we quantified IgA and IgG coating in FM patients and controls (n = 50–60/group). We then used fluorescent activated cell sorting to isolate IgG coated and uncoated bacteria from FM and control stool samples (n=32/group). DNA was extracted and sequenced using long-read 16s rRNA Nanopore sequencing, which allows for species identification. The sequencing data was aligned with Emu5 and analyzed using DESeq2.

Results: FM patients had more gut bacteria coated with IgG compared to controls, but there was no difference in IgA coating. There were 7 gut bacterial species that were more abundant in FM patients. 67 species and 8 species were uniquely coated by IgG or IgA in FM. Additionally, 11 species had more IgG coating and 5 species had more IgA coating in FM patients compared to controls. There were also two bacterial species that were less coated by IgG in FM.

Conclusions: Altered IgG and IgA coating of distinct bacterial species in FM indicates that the FM gut microbiota is driving an abnormal adaptive immune response. The altered antibody response could give rise to the development of cross-reactive, pain-inducing autoantibodies.

References: 1. Minerbi, A. et al. Altered microbiome composition in individuals with fibromyalgia. PAIN 160, 2589 (2019).
2. Cai, W. et al. The gut microbiota promotes pain in fibromyalgia. Neuron 0, (2025).
3. Goebel, A. et al. Passive transfer of fibromyalgia symptoms from patients to mice. J Clin Invest 131, e144201.
4. Sterlin, D., Fadlallah, J., Slack, E. & Gorochov, G. The antibody/microbiota interface in health and disease. Mucosal Immunol 13, 3–11 (2020).
5. Curry, K. D. et al. Emu: species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data. Nat Methods 19, 845–853 (2022).
6. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550 (2014).

Presenting Author: Ezrah Isaac Roy
Submitting Author: Ezrah Isaac Roy

Senior Author: Emerson Krock

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Hannah Cho - McGill
• Patrick Lypaczewski - McGill
• Caroline Monat - McGill
• Alexander Rosenström - Uppsala University
• Karolina af Ekenstam - Karolinska Institutet
• Monika Löfgren - Karolinska Institutet
• Emilie Linderoth - Karolinska Institutet
• Katalin Sandor - Karolinska Institutet
• Camilla I. Svensson - Karolinska Institutet
• Benoit Cousineau - McGill
• Eva Kosek - McGill
• Emerson Krock - McGill