Gut microbiome variation across fibromyalgia symptom severity

Abstract Background Fibromyalgia (FM) is a chronic pain syndrome with heterogeneous clinical manifestations that complicate diagnosis. Although biomarkers could improve diagnostic accuracy, their identification has been limited by the disease’s multifactorial nature. Growing evidence suggests that alterations in the gut microbiota may contribute to FM, but findings across cohorts remain inconsistent, and their relationship with symptom severity has not been characterized. Methods Here, gut microbiome composition was analyzed using 16 S rRNA gene sequencing in 101 female participants (51 healthy controls and 50 patients with FM). Symptom severity was assessed using the Fibromyalgia Severity Scale (FSS), and patients were stratified to enable comparisons across severity levels. Results While dominant phyla and families were preserved, significant diversity differences were observed. Beta diversity differences were more pronounced in severity-stratified analyses than in aggregate FM versus control comparisons. Reduced alpha diversity was restricted to the intermediate-severity group. Eubacterium hallii was consistently depleted in FM, including in the overall cohort and in intermediate and severe strata, while Bifidobacterium and Clostridia UCG-014 were reduced in the intermediate group. Conclusions These findings suggest that microbiome alterations in FM are associated with symptom severity and follow a non-linear pattern, underscoring the importance of symptom stratification in microbiome studies.