Gastrointestinal disorders associated with migraine: A comprehensive review

Table 1 Summary of gastrointestinal disorders associated with migraine

GI disorder	Association	Proposed implicated mechanism	Clinical implication
H. pylori infection	Infection rate of H. pylori: 45% in PWM vs 33% in controls[20]	Chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system	Screening of H. pylori infection in patient with migraine
	Main affected:
	CagA-positive strains[17]	↑ Interleukin-10 (CagA-positive strains)[25]	Improvement of migraine with H. pylori eradication[17,18,22]
	Asian > Europeans[20]	↑ CGRP[28]
Irritable bowel syndrome	6%-32% migraine-type headache in IBS patients vs 2.2%-18% in controls[33,35,36]	The brain-gut axis and the intestinal microbiota have been postulated[30,95]	Improvement of migraine with elimination diet[40]
		Serotonin, biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network[30]
Gastroparesis	During a migraine attack gastric emptying delay and impairment of drug absorption has been demonstrated[44,45]	↑ Sympathetic response[43]	Increase absorption of antimigraine agents by administering antidopaminergic and 5-HT4 agonists with antiemetic/prokinetic properties[46]
		↓ Parasympathetic tone[43]
		Dysfunction of enteric autonomic system[41,47]
Hepato-biliary disorders	Association between migraine and biliary tract disorders[60]	CCK has been found to coexist with CGRP in the trigeminal ganglion[63]. When stimulated induce local increase of CCK which has a vasodilatory effect[63,66]. CGRP has shown to influence biliary motility. The impaired CGRP release has been associated to biliary tract disease in humans[65]	Low-fat diet improves frequency and severity of migraine[73]
	Genetic influence:
	In monozygotic pairs (OR = 3.5)
	In dizygotic pairs (OR = 1.7-2.7).
	Among the migraine characteristics, in those PWM with NAFLD, the presence of aura was higher (73.6% vs 26.5%), and the disease (9 yr vs 6 yr) and attack (72 h vs 48 h) durations were longer than in those without NAFLD[68]. Obesity and metabolic disturbances which are important determinants of NAFLD are also associated with an increased risk of migraine[69,70]		In connection with NAFLD: Weight loss and metabolic control have shown to improve migraine[70]
Celiac disease	28% prevalence of migraine in subject with biopsy-proven CD[84]	Neurological complications in CD may be caused by a general inflammatory response[92]	The screening for migraine in patients with CD seems to be justified.
	Higher prevalence of migraine in biopsy-proven CD group than in controls (21% vs 6%, OR = 3.79)[85]	Elevated levels of interferon-gamma and TNF-alpha (both independently implicated in migraine and CD) modulate neuropeptide CGRP[93].	Possible therapeutic effect with gluten-free diet[86-89]
	Main affected:
	Female
	Age < 65

GI: Gastrointestinal; PWM: Patients with migraine; CGRP: Calcitonin gene-related peptide; IBS: Irritable bowel syndrome; CCK: Cholecystokinin; NAFLD: Non-alcoholic fatty liver disease; CD: Celiac disease; TNF: Tumor necrosis factor.