Fibromyalgia and the Gut Microbiome: Current Evidence, Mechanistic Insights, and Research Priorities

Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, frequently accompanied by fatigue, sleep disturbances, and cognitive dysfunction. Studies have identified differences in gut microbial composition and metabolite profiles in some FM cohorts, but their consistency, clinical significance, and causal direction remain uncertain. This critical narrative review evaluates human observational evidence, experimental models, and microbiome-targeted interventions, distinguishing findings directly relevant to FM from mechanistic insights derived from other conditions. Particular attention is given to short-chain fatty acids (SCFAs), tryptophan metabolism, and bile acids as potential mediators of host–microbiome interactions along the gut–brain axis. Human studies are limited by small, predominantly female cohorts, inconsistent findings, and confounding related to gastrointestinal conditions, diet, medication use, and intestinal transit. Although transfer of FM-associated microbiota can induce pain-related phenotypes in experimental animals, these findings do not establish disease causation in humans. Evidence for dietary interventions, probiotics, and fecal microbiota transplantation remains preliminary, with unresolved questions concerning efficacy, safety, and durability. We also propose a hypothetical framework of overlapping immune, metabolic, and neuroendocrine or stress-related domains to guide future investigation, not to define validated FM endotypes. Multi-omics and artificial intelligence (AI) may help test these hypotheses, but clinical applications require longitudinal research, independent validation, and adequately controlled trials.