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The role of protein digestibility and antacids on food allergy outcomes

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Digestion assays with simulated gastric fluid have been introduced for characterization of food proteins to imitate the effect of stomach proteolysis on dietary compounds in vitro. By using these tests, dietary proteins can be categorized as digestion-resistant class 1 (true allergens triggering direct oral sensitization) or as labile class 2 allergens (nonsensitizing elicitors). Thus the results of these digestion assays mirror situations of intact gastric proteolysis. Alterations in the gastric milieu are frequently experienced during a lifetime either physiologically in the very young and the elderly or as a result of gastrointestinal pathologies. Additionally, acid-suppression medications are frequently used for treatment of dyspeptic disorders. By increasing the gastric pH, they interfere substantially with the digestive function of the stomach, leading to persistence of labile food protein during gastric transit. Indeed, both murine and human studies reveal that antiulcer medication increases the risk of food allergy induction. Gastric digestion substantially decreases the potential of food proteins to bind IgE, which increases the threshold dose of allergens required to elicit symptoms in patients with food allergy. Thus antiulcer agents impeding gastric protein digestion have a major effect on the sensitization and effector phase of food allergy.

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Food antigen absorption: A delicate balance between oral tolerance and induction of immune responses

During human evolution, a sophisticated safety system developed to simultaneously allow immune defense against pathogens and avoidance of hypersensitivity reactions against harmless substances, such as food. The mucosal barrier, consisting of intestinal epithelial cells joined together by apical and basolateral tight junctions and mucus produced by specialized epithelial cells, such as goblet cells, prevents antigen penetration.16 Additionally, immunologic mechanisms, including immune exclusion

Physiologic digestion of dietary proteins

After a relatively quick passage through the esophagus, proteins contained in the macerated food bole enter the gastric lumen. Here the stomach is distended by the entering food, resulting in increased gastrin secretion. Absorbed from the blood stream, gastrin triggers hydrochloric acid production in the parietal cells and, to a lesser extent, digestive enzyme secretion by the chief cells of the gastric glands.33 In the stomach the chyme is not only exposed to hydrochloric acid, mucins, and

Classification of food allergens

Only dietary proteins large enough to elicit immune responses are potential food allergens. It has been hypothesized previously that protein epitopes recognized by IgE antibodies are of conformational nature,47, 48 which we recently confirmed for the IgE-binding site of the major fish allergen parvalbumin,49 as well as for other allergens.50, 51, 52 However, on chronic allergen exposure, such as in milk allergy, linear epitopes might become important in later stages of the disease.53

Predicting the allergenic potential of food proteins by using digestion assays

Based on current knowledge on the relation of gastrointestinal digestion, food allergy, and dietary allergens, digestion experiments have been introduced for assessing the allergenic capacity of novel food proteins. In 1996, Astwood et al62 reported in a cutting-edge study that digestion experiments in simulated gastric fluid (SGF) ideally distinguish between potentially allergenic and nonallergenic food proteins. Their work was triggered by reports on common characteristics of food allergens63

Physiologically and pathologically altered gastric digestion capacity

Interestingly, gastric digestion assays only simulate situations in which both the production of digestive enzymes and the acid-secretion capacity of the stomach are intact. It is noteworthy that the secretory capacity of the stomach changes physiologically throughout a lifetime, influencing gastric protein digestion. Early studies indicated that in newborns the intragastric pH ranges from 6.0 to 8.0,81, 82 which is followed by a burst of acid secretion leading to adult gastric pH levels (pH

Acid suppression medication: Worldwide prescription habits, mechanisms of action, and possible side effects

From their broad application in clinics, it is not surprising that antiulcer agents are among the top-selling drugs worldwide. The use of antiulcer medication is rapidly increasing in Western countries and comprises up to 10% of the national medical budget.103, 104, 105, 106 In 1996, 2% of the English health authority budget was spent on acid-suppression drugs, with 80% of the costs being caused by repeated prescriptions without further medical consultation.107, 108, 109 Despite clear

Interference with gastric digestive capacity represents a risk factor for food-induced allergic reactions

When gastric digestion experiments with digestion-labile food allergens, such as fish, milk, or hazelnut, were performed with SGF pH at 5.0, these allergens remained stable, even for 2 hours.27, 77, 78, 79 Titration experiments revealed that the enzymatic capacity of pepsin contained in SGF was completely eliminated when the pH was increased to 2.75 in the case of codfish and to 3.0 for milk proteins.77, 78 Additionally, RAST inhibition experiments showed the IgE-binding capacity of fish

Safety issues and clinical implications for allergic and nonallergic consumers

The data reviewed here suggest that the immunologic or clinical outcome after the consumption of a digestion-sensitive dietary protein depends to a certain degree on the gastric digestive capacity. If the food protein is exposed to gastric enzymes during transit, protein cleavage takes place, inducing either oral tolerance or immune ignorance toward the ingested food protein. However, if proteins persist during the gastric transit because of impaired digestion, such as during acid-suppression

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    Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD

    Supported by grant 11375 of the Austrian National bank “Jubiläumsfond” and by grants H220-B13 and SFB F1808-B13 of the Austrian National Science Foundation (FWF).

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