analysis identified protective associations between and four gut microbiota taxa.
Four gut microbiota taxa were found to have protective associations with fibromyalgia.
Risk associations with fibromyalgia were identified for two specific gut microbiota genera.
Eighty-two plasma metabolites were linked to fibromyalgia and involved in pathways such as caffeine and α-linolenic acid metabolism.
Mediation analysis suggested that two specific metabolites influenced the risk of fibromyalgia.
Personalized dietary interventions such as reducing caffeine and increasing omega-3 fatty acids may alleviate symptoms associated with fibromyalgia.
Simplified
(FM) is a complex disorder characterized by chronic pain, fatigue, and functional impairments, with unclear pathological mechanisms. Gut microbiota and plasma metabolites have been implicated in FM, but their causal relationships remain unexplored. This study aims to assess the causal relationships between gut microbiota, plasma metabolites, and FM using (MR) analysis and to explore potential mediating mechanisms. Public genome-wide association study data were analyzed using bidirectional MR. Associations between gut microbiota, plasma metabolites, and FM were evaluated, and multivariable MR identified mediating metabolites. Results were validated with inverse variance weighted, MR-Egger, and weighted median methods, with metabolic pathway enrichment analysis for further insights. MR identified protective associations between FM and four taxa (family, genus, genus, and order) and risk associations with genusand genus. Additionally, 82 plasma metabolites linked to pathways such as caffeine metabolism, α-linolenic acid metabolism, GLP-1, and incretin regulation were associated with FM. Mediation analysis revealedandinfluenced FM risk through 2,3-dihydroxypyridine and palmitoylcholine. Personalized dietary interventions, such as limiting caffeine intake, increasing omega-3 fatty acid consumption, adopting a low glycemic index diet, and reducing the intake of high-oxalate foods, may effectively alleviate FM-related symptoms by modulating metabolic pathways, reducing inflammation, and mitigating oxidative stress. This study highlights the intricate interactions between the gut microbiota and metabolic pathways, providing critical scientific evidence and actionable targets for clinical interventions, dietary management, and precision medicine approaches in FM treatment. Enterobacteriaceae Butyricicoccus Coprococcus1Enterobacteriales Eggerthella Ruminococcaceae UCG005Enterobacteriaceae Enterobacteriales
Key numbers
4
Protective Taxa
Four taxa show protective associations with .
2
Risk Taxa
Two taxa are associated with increased risk of .
82
Identified
Eighty-two linked to were identified.
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