Fibromyalgia

Metallomic Signature#

Mendelian randomization (MR) studies have identified a distinctive metal profile in FM, distinguishing causal relationships from mere associations:

The copper-iron axis is particularly informative: elevated copper competes with iron for transport and binding sites, potentially explaining the functional iron deficiency observed in FM patients even when serum iron appears normal.

Enriched Taxa#

Eggerthella—MR-validated causal taxon (OR = 1.897) Wang et al. 2024. Produces neurotoxic metabolites, activates pro-inflammatory pathways, and is enriched in multiple neuropsychiatric conditions.

Flavonifractor—enriched in FM; associated with oxidative stress and depression. Coprococcus 2—MR causal association (OR = 2.317) Wang et al. 2024; paradoxically a butyrate-associated genus, suggesting strain-level functional divergence. Streptococcus salivarius—enriched in oral and gut communities of FM patients.

Collinsella—pro-inflammatory; enriched in rheumatoid arthritis and FM.

Central Sensitization and the Gut-Brain Axis#

Central sensitization in FM is not merely a CNS phenomenon—it is driven in part by peripheral signals from the gut. Tryptophan-serotonin pathway dysfunction: Dysbiotic communities shunt tryptophan toward kynurenine (via IDO upregulation from pro-inflammatory cytokines), reducing serotonin availability and generating neurotoxic quinolinic acid.

Glutathione depletion: GPX3 decreased 0.85x in FM patients Duran-Gonzalez et al. 2025, reducing capacity to neutralize oxidative stress from copper excess and microbial metabolites.

LPS translocation: Barrier dysfunction permits endotoxin entry, activating TLR4 on microglia and amplifying neuroinflammation. SCFA signaling disruption: Reduced butyrate at the colonocyte impairs vagal afferent signaling, disrupting the anti-inflammatory cholinergic pathway.

Metal Associations#

The metallomic signature intersects with microbiome ecology through multiple mechanisms. Copper excess promotes oxidative stress that selectively favors copper-tolerant taxa (Eggerthella, Collinsella) while suppressing copper-sensitive commensals.^{[1]Impact of heavy metals on serum vitamin D3 and PTH in fibromyalgia and rheumatoid arthritis and their correlation to disease activityHaddad R, Elbeialy A, El Sawy S et al. · 2024Open reference 1 ↓}

Iron restriction by hepcidin starves iron-dependent beneficial taxa (Faecalibacterium requires iron for butyrate synthesis) while sparing iron-independent opportunists. Magnesium depletion impairs enzymatic function in both host tissues and commensal bacteria. Selenium depletion reduces glutathione peroxidase activity, amplifying oxidative damage from copper excess.