Roles of gut microbiota metabolites in the pathogenesis of migraine

Migraine is one of the most common neurological disorders, with a complex and incompletely understood pathogenesis. Recent studies have implicated the gut-brain axis in migraine pathophysiology. The gut microbiota and microbiota-related metabolites may influence migraine-related processes through neural, immune, endocrine, and metabolic pathways. This review summarizes the potential roles of microbiota-derived metabolites in migraine through the gut-brain axis, with a focus on short-chain fatty acids (SCFAs), tryptophan (Trp)-related metabolites, and nitric oxide (NO)-related metabolic pathways, and their potential effects on neuroimmune signaling, intestinal barrier integrity, and trigeminovascular function. Current evidence suggests that gut dysbiosis and metabolic disturbances are associated with migraine and may modulate neuroinflammatory pathways and central sensitization; however, direct causal evidence in humans remains limited. Interventions targeting the gut microbiota or related metabolic pathways, including probiotics and dietary modifications, may represent potential adjunctive strategies, although current clinical evidence remains limited and heterogeneous.