Migraine

Overview

Migraine is a complex neurological disorder characterized by recurrent episodes of moderate-to-severe headache, often unilateral and pulsatile, accompanied by nausea, photophobia, and phonophobia. Affecting over one billion people worldwide, it is the second leading cause of disability globally. The gut brain axis is increasingly implicated in migraine pathophysiology.

Microbiome Associations

Migraine patients show altered gut microbiome composition, with enrichment of nitrate-reducing bacteria — organisms that convert dietary nitrate to nitrite and nitric oxide (NO). Excess NO is a known migraine trigger through vasodilation and CGRP release. Taxa enriched in migraine include certain Streptococcus and Haemophilus species. Depletion of butyrate-producing Faecalibacterium and Roseburia has also been reported, suggesting impaired gut barrier function.

Metal Associations

Magnesium deficiency is one of the most consistent findings in migraine, present in up to 50% of patients during attacks. Magnesium modulates NMDA receptor excitability and serotonin receptor function. Iron metabolism is altered — serum ferritin levels correlate inversely with migraine frequency in some studies. Copper and zinc imbalances have been reported but findings are inconsistent.

Associated Conditions

Migraine shows strong comorbidity with irritable-bowel-syndrome (shared gut-brain axis dysfunction), depression (serotonin pathway overlap), celiac disease (gluten as trigger, shared nutrient malabsorption), and Helicobacter pylori infection. The gut-brain overlap suggests shared microbial and metabolic underpinnings rather than coincidental co-occurrence.

Open Questions

Whether microbiome-targeted interventions (probiotics, dietary modification of nitrate intake) can reduce migraine frequency remains an active area of clinical investigation with preliminary but encouraging results.

Cross-References

References (5)

  1. Park JC, Chang L, Kwon HK et al. (2025). Beyond the gut: decoding the gut-immune-brain axis in health and disease. Cellular and Molecular Immunology. doi:10.1038/s41423-025-01333-3
  2. Zheng J, Tao L (2025). Multidimensional mechanisms and therapies underlying gastroesophageal reflux disease: focus on immunity, signaling pathways, and the microbiota-gut-brain axis. Frontiers in Immunology. doi:10.3389/fimmu.2025.1629944
  3. Shen Z, Bian Y, Huang Y et al. (2024). Migraine and gastroesophageal reflux disease: Disentangling the complex connection with depression as a mediator. PLoS ONE. doi:10.1371/journal.pone.0304370
  4. Larissa Hauer, Julian Perneczky, Johann Sellner (2021). A Global View of Comorbidity in Multiple Sclerosis: A Systematic Review with a Focus on Regional Differences, Methodology, and Clinical Implications. Journal of Neurology. doi:10.1007/s00415-020-10107-y
  5. Yang F, Xie XH, Li X et al. (2022). Analysis of Psychological and Gut Microbiome Characteristics in Patients With Non-erosive Reflux Disease. Frontiers in Psychiatry. doi:10.3389/fpsyt.2021.741049