Oral–gut–brain axis in migraine: A new frontier in neuroinflammation and microbial therapeutics

Migraine is a multifaceted neurovascular condition impacting more than one billion people worldwide. Historically attributed to the trigeminovascular system and neuropeptide imbalance, recent developments indicate a substantial involvement of microbial populations in the pathogenesis of migraines. This review analyses contemporary evidence connecting the oral, intestinal and nasal microbiota to migraine through immunological, vascular and neurological pathways. The gut microbiome affects central sensitisation, vagus nerve activation and blood–brain barrier permeability. Salivary microbiota, especially nitrate-reducing species, may influence nitric oxide pathways, thereby impacting cerebral vasodilation. Alterations in nasal microbiota may influence trigeminal and olfactory signalling, presenting an additional microbial pathway to neuroinflammation. We examine evidence from multi-omics research, Mendelian randomisation and observational cohorts, indicating that the oral–gut–brain axis is a feasible target for therapeutic intervention in migraine. We will conclude by examining the prospects of microbial therapies and biomarker identification in individualised migraine treatment.