The gut microbiota promotes pain in fibromyalgia 2025 Khoutorsky et al

Andy

Andy

Retired committee member
Highlights

• Transplanting gut microbiota from women with fibromyalgia into mice induces pain
• It also induces immune activation, metabolomic changes, and reduced skin innervation
• Gut microbiota promotes pain through several mechanisms

Summary

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.

Open access
 
It’s important to note that they had to use antibiotics prior to the FMT, so this might not be a viable treatment if we’re concerned about super-bacteria.

On mice:
Transplantation of HC microbiota into FM microbiota-recipient mice, after antibiotic pretreatment, induced a shift in the bacterial composition of the gut microbiota (Figures S13A and S13B), and this shift was diminished if antibiotics were omitted.
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Notably, HC FMT into FM microbiota-recipient mice without prior suppression of gut communities with antibiotics failed to alleviate pain (Figures 5B–5E). Antibiotic treatment alone slightly reduced mechanical hypersensitivity but had no effect on heat and cold hypersensitivity or spontaneous pain (Figures 5B–5E)
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The open-label pilot:
Following depletion of the endogenous microbial communities using antibiotics and bowel cleansing, patients received five FMTs, once every 2 weeks, via oral administration of encapsulated transplants from healthy donor
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The paper said:
An open-label trial in women with fibromyalgia
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What a difference in framing and presentation from the usual. This is how it should be presented. There is far too much marketing language allowed in EBM. It would make a huge difference if it were all described neutrally, using common terms and caveats.

All the difference between running a major story on page A1 above the fold in a major newspaper, vs page A18 of the week-end edition, featuring an odd headline that twists and hides the story.

Also a correct framing of what promising means: let's get more rigorous with it over time, but no one should use this right now. Not: let's jump all the guns and use it as standard practice because it must be correct (since we want it to be), as is standard in biopsychosocialand.
 
Jonathan Edwards said:
As usual I would be more inclined to read this if they gave some actual data in the abstract.
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Here is some data from the text.
Metabolomic changes in mice colonized with FM microbiota
Gut microbiota can affect metabolomic profile and immune function, both of which are dysregulated in FM patients.12,13,15,42 Using untargeted metabolomic analysis, we found that mice that received FM FMT exhibited an altered metabolomic profile compared with mice that received FMT from HCs. We detected changes in the metabolism of neuroactive amino acids, including increased levels of glutamine in the spinal cord, and elevated glutamate in the brain (Figure S8; Data S2). Lipid metabolism was also dysregulated in FM FMT-recipient mice, as they exhibited a decrease in medium and long-chain fatty acids, branched-chain fatty acids, and dicarboxylate fatty acids in plasma (Figure S8). Moreover, we found alterations in secondary bile acid metabolism, including a decrease in the bile acid ursocholate in plasma (and increased lithocholic acid sulphate in the feces).
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Immune alterations in mice colonized with FM microbiota
An analysis of the immune landscape, conducted using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) (Figures 3A, S10A, and S10B), revealed that mice colonized with FM microbiota had an increased proportion of classical monocytes compared with mice that received HC FMT (Figures 3B and 3C). Analysis of differentially expressed genes within this cellular population showed enrichment for IL-17 and tumor necrosis factor (TNF) signaling pathways, which are associated with inflammatory responses (Figure 3D). Immune-related changes were also present in other cell types, including intermediate/non-classical monocytes, memory/plasma B cells, dendritic cells, Treg, and B-cell-like T cells (Data S3). The proportion of memory B cells was decreased in FM FMT-recipient mice (Figure S10C).
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