Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development

Abstract

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Keywords: IgE; allergy; animal models; clinical test; enzyme hydrolysis; fermentation; gluten hypersensitivity; preclinical test; therapeutics; translational research; wheat.

Figure 1

Pathogenesis of gluten hypersensitivity: the role of genetics and environmental factors. Inheritance of susceptibility gene variants from parents renders the offspring a propensity to develop atopic sensitization to gluten that is modulated by co-exposure to environmental factors. Some of the known genetic and environmental factors are illustrated in the figure. Re-exposure to gluten results in the development of gluten hypersensitivity reactions. The routes of sensitization can be oral, skin, eyes, and airways. The routes of disease elicitation can be oral, skin, eyes, airways, and blood transfusion. Exercise upon ingestion of gluten can result in WDEIA within one to four hours. WDEIA: wheat-dependent exercise-induced anaphylaxis; FA: food allergy; LTSA: life-threatening systemic anaphylaxis; AD: atopic dermatitis; U: urticaria; AC: allergic conjunctivitis; AAD: allergic airways disease; BA: baker’s asthma; IgE: immunoglobulin E.

Figure 2

Key steps in traditional soy sauce production and the progressive reduction in and elimination of gluten and non-gluten allergens. This figure shows the various steps involved in soy sauce production. The effects on gluten and non-gluten allergens based on the research reported in the literature are also summarized. The salt-soluble non-gluten allergen content as measured by direct ELISA is progressively reduced by approximately 68%, 86%, 89%, and undetectable by the end of step 2, koji, moromi day 10, and moromi day 48, respectively, as measured by direct ELISA. The salt-insoluble wheat allergen (gluten) content as measured by direct ELISA is progressively reduced by approximately 32%, 91%, 96%, and undetectable by the end of step 2, koji, moromi day 10, and moromi day 48, respectively, as measured by direct ELISA.