Review Outlines Relationship Between Gut-Brain Axis, Migraine

The associations between migraine and several gastrointestinal (GI) disorders promtped investigations into the bidirectional relationship between the GI system and central nervous system (CNS). Researchers call this association the “gut-brain axis,” and they evaluated direct and indirect evidence linking migraines to the axis in a recent review published in The Journal of Headache and Pain.

Several factors including inflammatory mediators, neurotransmitters, gut microbiota profile, neuropeptides, stress hormones, and nutritional substances have been studied in an effort to support a concrete link between the 2 systems. The researchers also note disorders including Helicobacter pylori infection, irritable bowel syndrome (IBS), celiac disease (CD), and inflammatory bowel disease (IBD) have been associated with migraine.

The review highlights roles of 2 neuropeptides in particular: neuropeptide Y (NPY) and cholecystokinin (CCK). NPY alters cerebral blood flow through cerebral circulation regulation. Higher levels of NPY have also been detected in the ictal phases of migraineurs, the authors said. “The NPY pathway is also assumed to contribute to the changing GI function and its blood flow, immunological system and inflammation status, pain, homeostasis of energy, emotion, mood, as well as behavior and other functions of the brain.”

CCK is synthesized by cells in the small intestine, brain, and spinal cord. The neuropeptide “inhibits gastric emptying and acid secretion…and provokes satiety feeling in the brain via CCK1 receptors.” One explanation for why obese individuals expericence higher frequency and severity of migraine is secretion of CCK "in response to high fat diets as intraduodenal free fatty acids."

Comorbidities involving GI disorders are common among migraineurs. The review found:

• In a meta-analysis of 5 case control studies, 45% of migraineurs harbor H pylori
• A prevalence cohort study found patients with IBS had a 40% to 80% higher prevalence odds of migraine, depression, and fibromyalgia
• Migraineurs with long headache history and high headache frequency had a higher chance of an IBS diagnosis
• About 21% to 28% of patients with CD have migraine
• According a case control study, the prevalence of headache was 46% in individuals with IBD compared with 7% in a control group

The researchers note that probiotic supplementation may benefit migraineurs. One randomized double-blind controlled trial included in the review found “probiotic administration resulted in significant improvements in frequency and severity of migraine,” along with decreased usage of abortive medications. Participants exhibited these improvements despite there being no significant changes in serum levels in observed inflammatory biomarkers.

Another effective dietary adjustment was the switch to low-fat diets. The researchers found “reducing dietary intake for 3 months resulted in the reduction in headache intensity, frequency, and abortive medication consumption.”

Although specific mechanisms underlying the relationship is unclear, the researchers hypothesize dietary approaches can have beneficial effects on the gut-brain axis and gut microbiota and could lead to improvements in migraine symptoms.

Reference

Arzani M, Jahromi SR, Ghorbani Z, et al; School of Advanced Studies of the European Headache Federation (EHF-SAS). Gut-brain axis and migraine headache: a comprehensive review. J Headache Pain. 2020;21(1):15. doi: 10.1186/s10194-020-1078-9.