Reducing the incidence of allergy and intolerance to cereals

Gilissen, L.J.W.J.; Meer, I.M. van der; Smulders, M.J.M.


During recent decades, allergies and certain food intolerances have shown a worldwide gradual increase in prevalence, concomitantly with economic growth, urbanization, and changes in lifestyle and dietary patterns. They are triggered in humans with an unbalanced immune system and intestinal micro-flora by specific animal and plant proteins present in a variety of foods including cereals. Allergies are generally violent immune reactions, whereas symptoms of intolerances are mainly chronic. Cereals contain various types of proteins, including water-soluble albumins, saline-soluble globulins, alcohol-soluble prolamins, and insoluble glutenins. The absolute and relative amounts of these protein types vary considerably among cereals, as do their digestibility and immunogenicity The prevalence of allergies to cereals is low, although no exact frequencies are known. Most commonly mentioned, and described in this review, are allergies to wheat, maize and rice, of which occupational bakers’ asthma has the highest economic impact. Lipid transfer protein, ¿-5-gliadin and amylase trypsin inhibitor, all related proteins in the prolamins superfamily, are the causal proteins. Sensitization (i.e. the presence of specific IgE in serum without clinical symptoms) involves a wider variety of protein types, mainly known from wheat, and affects about 2% of the population. Sensitizing and allergenic proteins are generally identified through IgE binding. Cereal intolerance occurs at a prevalence of 1-3% of the population worldwide, but varies between countries. The causal proteins are the gliadins and the glutenins from wheat and related proteins from barley and rye, together commonly called ‘gluten’. Gluten intolerance (or coeliac disease, CD) is classified as an auto-immune disease and occurs in individuals with the human leucocyte antigen (HLA) DQ2 and/or DQ8 genotype. The increase of wheat gluten consumption, especially through the worldwide increased application of ‘vital gluten’ in a broad variety of food products and through increased consumption of wheat flour-based products, may have contributed to the increased prevalence of CD during the last decades since the 1950s. Recently, rapid and significant growth has been observed in the number of consumers embracing a gluten-free or wheat-free diet. No clear and unambiguous medical and scientific symptoms are yet available to consider this so-called ‘non-coeliac gluten sensitivity’ (ncGS; also known as non-coeliac wheat sensitivity, ncWS) as a new health threat. A correlation with IBS (Irritable Bowel Syndrome) is suggested. To develop strategies for reduction of the incidence of cereal allergy and intolerance, we review the most up to date information on (1) the diagnosis of the diseases and (2) the detection and characterization of the relevant proteins. Cereal allergies are reliably tested by skin-prick tests and (double-blind placebo-controlled) food challenges. For ncGS, a wheat/gluten elimination diet is currently the only diagnostic tool. CD is diagnosed according to five well-defined criteria, but it is thought that only about 10% of the total CD population has been diagnosed properly. Because of the chronic character and the high diversity of the symptoms, misdiagnosis often occurs. Many undiagnosed individuals, unaware they may have CD, accept their chronic state of ill health as normal. Nevertheless, this large group forms a significant societal issue in terms of prevention In CD, the gliadins and glutenins form a complex mixture of proteins from different protein families, of which most carry one or more of the 31 internationally agreed HLA-DQ2 and –DQ8 epitopes. Measuring CD toxicity depends on the identification and quantification of the immunogenicity (number and clinical impact of the various epitopes) of a cereal cultivar or a cereal-derived food product. By far the most CD-toxic epitopes are known from the gliadins (especially from the a-gliadins). Diagnostic tools available are monoclonal antibodies, T cells, genomics and proteomics analysis, and reference material and volunteers are required. Knowledge built on diagnostic and detection/characterization data enables the development of a framework to design and implement prevention strategies at the primary, secondary and tertiary levels. We have reviewed in particular the possibilities for prevention by (1) searching for low CD-toxic wheat varieties via selection, breeding, mutation and genetic modification (deletion and silencing of gluten gene loci); (2) production of safe cereal foods through processing and other technological approaches, such as sourdough fermentation, specifically removing gliadins from gluten extracts, the development of gluten alternatives for applications in food improvement, and increasing the overall quality and reliability of gluten-free food products; and (3) the introduction of safe alternative cereals into the gluten-free diet, with special emphasis on oats. These strategies may result in better balancing of, in particular, the use of wheat (gluten) with food safety. In this regard, the overall growing interest in gluten-free foods should be considered a positive challenge to the food industry for product-innovation. A sustainable reduction in the incidence and the prevalence of immune-related diseases, including cereal allergy and intolerance, will require increasing the knowledge and understanding of the interactions between the three major pillars: the food (eating pattern and lifestyle), human genetics and physiology, and the intestinal micro-flora