Articles
Oral Tolerance and its Relation to Food Hypersensitivities

J Allergy Clin Immunol, Jan 2005: 3-12 - Mirna Chehade, MD and Lloyd Mayer, MD

The Gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens.  Once proteins contact the intestinal surface, they are sampled  by different cells and depending on their characteristics, result in different responses. Antigens might be taken up by the Microfold cells overlying Peyer’s patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related and other are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerances and cite data related to food hypersensitivity wherever evidence is available.

Gastroenterology, 2007 Mar;132(3):913-20.  Liebregts T, Adam B, Bredack C, Röth A,et al.

Researchers test the hypothesis that irritable bowel syndrome is characterized by a cellular immune response with the production of proinflammtory cytokines and also explore psychiatric symptoms associated with IBS.  IBS-D patients who had greater than 3 bowel movements per day with watery stools, pain and cramping showed significantly higher cytokine levels in all categories, with accompanying anxiety.
***Cytokine activation is indicative of an immune response:

Prog Med 1989 Feb;80(2):53-5. Pacor ML, Nicolis F, Cortina P, Peroli P, Venturini G, Andri L, Corrocher R, Lunardi C.

Migraine was present in 41 out of 300 patients (13.6%). 38 of these 41 subjects had been treated with elimination diets; 25 (65.7%) obtained a significant improvement of migraine on subsequently performed challenge test. 24 patients were affected by food intolerance and only one by food allergy. The remaining 13 non-responder subjects suffering from migraine had been subsequently submitted to pharmacological treatment.

Acta Neurol (Napoli) 1991 Oct;13(5):448-56. Mertelletti, P

A group of migraine patients were studied for circulating immune complexes, lymphocyte subpopulations, IgG4 and anti-IgG antibodies, before, after 4 hours and after 72 hours a specific challenge test. 

There was an  increased incidence of circulating immune complexes. Total T cells showed a marked increase after challenge test. The most important finding was the presence of T-activated cells. Also K and NK cells showed an early increase after the challenge. 

In commenting on the outcomes of this investigation, it must be stressed that the evidence of an early lymphocyte activation after the challenge test indicates an involvement of interleukin-2 related receptor in food-induced migraine. 

The results have reinforced the idea of immune mechanism involvement in food-induced migraine, but it seems to be a different mechanism from that previously hypothesized, with the involvement of the “complex cytokines."

Millichap JG, Yee MM. Pediatr Neurol 2003 Jan;28(1):9:15

Division of Neurology; Children's Memorial Hospital; and Northwestern University Medical School;, Chicago, Illinois, USA

Diet can play an important role in the precipitation of headaches in children and adolescents with migraine. The diet factor in pediatric migraine is frequently neglected in favor of preventive drug therapy. The list of foods, beverages, and additives that trigger migraine includes cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine withdrawal, and alcoholic drinks, especially red wine and beer. Underage drinking is a significant potential cause of recurrent headache in today's adolescent patients. Tyramine, phenylethylamine, histamine, nitrites, and sulfites are involved in the mechanism of food intolerance headache. Immunoglobulin E-mediated food allergy is an infrequent cause. Dietary triggers affect phases of the migraine process by influencing release of serotonin and norepinephrine, causing vasoconstriction or vasodilatation, or by direct stimulation of trigeminal ganglia, brainstem, and cortical neuronal pathways. Treatment begins with a headache and diet diary and the selective avoidance of foods presumed to trigger attacks. A universal migraine diet with simultaneous elimination of all potential food triggers is generally not advised in practice. A well-balanced diet is encouraged, with avoidance of fasting or skipped meals. Long-term prophylactic drug therapy is appropriate only after exclusion of headache-precipitating trigger factors, including dietary factors.

A Gut Check For Many Ailments

"The gut is important in medical research, not just for problems pertaining to the digestive system but also problems pertaining to the rest of the body," says Pankaj J. Pasricha, chief of the division of gastroenterology and hepatology at Stanford University School of Medicine.

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