Rye Proteins Research Articles

Use of Quinoa Flour in The Production of Gluten-Free Tarhana

Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Gluten is a complex mixture of storage proteins of wheat, rye and barley. However, pseudocereals do not contain gluten. Quinoa -one of three pseudocereals- has high level of protein, fat, fiber, vitamin, mineral and micro constituents, low level carbohydrate and it has good amino acid balance. The purpose of this study was to make gluten-free tarhana by using different ratios (40:30:30, 50:25:25 and 60:20:20%) quinoa flour (QF), rice flour and potato starch instead of wheat flour, and to determine the effects of QF addition levels on the some physical, chemical, nutritional, sensory properties of tarhana samples. The use of QF led to a decrease in fermentation loss values of the tarhana samples. Also, QF affected the colour (L*, a* and b*) of gluten-free tarhana. The tarhana samples containing 60% QF had the highest a* values, while tarhana samples containing 40% QF had the highest b* values. The use of high level QF (60%) increased crude protein, ash, crude fat, potassium, magnesium, calcium and iron contents in tarhana samples. Moreover, QF affected the scores of sensory properties of gluten-free tarhana soups. Tarhana soups prepared with 50% QF gave the highest scores for consistency and overall acceptability. In conclusion, gluten-free tarhana were satisfactorily improved in terms of chemical, nutritional and sensory properties nutritional properties by quinoa flour.

Changes of Detergent-Resistant Plasma Membrane Proteins in Oat and Rye during Cold Acclimation: Association with Differential Freezing Tolerance

Cold acclimation (CA) results in an increase in freezing tolerance of plants, which is closely associated to functional changes of the plasma membrane (PM). Although proteomic studies have revealed compositional changes of the PM during CA, there has been no large-scale study of how the microdomains in the PM, which contains specific lipids and proteins, change during CA. Therefore, we conducted semiquantitative shotgun proteomics using microdomain-enriched detergent-resistant membrane (DRM) fractions extracted from low freezing-tolerant oat and highly freezing-tolerant rye. We identified 740 and 809 DRM proteins in oat and rye, respectively. Among the proteins identified, the abundances of a variety of proteins, such as P-type ATPase and aquaporins, were affected by CA in both oat and rye. Some CA-responsive proteins in the DRM fractions, such as heat shock protein 70, changed differently in oat and rye. In addition, changes in lipocalins and sugar transporters in the DRM fractions were different from those found in total PM fraction during CA. This is the first report to describe compositional changes in the DRM during CA. The proteomic profiles obtained in the present study hint at many possible microdomain functions associated with CA and freezing tolerance.

Targeted modification of wheat grain protein to reduce the content of celiac causing epitopes

The prolamin peptides in wheat gluten and in the homologous storage proteins of barley and rye cause painful chronic erasure of microvilli of the small intestine epithelium in celiac patients. If untreated, it can lead to chronic diarrhea, abdominal distension, osteoporosis, weight-loss due to malabsorption of nutrients, and anemia. In addition to congenital cases, life-long exposure to gluten proteins in bread and pasta can also induce development of celiac sprue in adults. To date, the only effective treatment is life-long strict abstinence from the staple food grains. Complete exclusion of dietary gluten is, however, difficult due to use of wheat in many foods, incomplete labeling and social constraints. Thus, finding alternative therapies for this most common foodborne disease remained an active area of research, which has led to many suggestions in last few years. The pros and cons associated with these therapies were reviewed in the present communication. As different celiac patients are immunogenic to different members of the undigestible proline/glutamine rich peptides of ~149 gliadins and low molecular weight glutenin subunits as well as the six high molecular weight glutenin subunits, an exhaustive digestion of the immunogenic peptides in the stomach, duodenum, jejunum, and ileum of celiacs is required. In view of the above, we evaluated the capacity of cereal grains to synthesize and store the enzymes prolyl endopeptidase from Flavobacterium meningosepticum and the barley cysteine endoprotease B2, which in combination are capable of detoxifying immunogenic gluten peptides in a novel treatment of celiac disease.

Repertoire of Gluten Peptides Active in Celiac Disease Patients: Perspectives For Translational Therapeutic Applications

Celiac disease is a common and lifelong food intolerance, affecting approximately 1% of the population. Because of a mechanism not completely understood, the ingestion of wheat gluten, and of homologue proteins of barley and rye, induces in genetically predisposed individuals pronounced inflammatory reactions mainly at the site of small intestine. Gluten, the triggering factor, is a complex protein mixture highly resistant to the gastrointestinal enzymatic proteolysis, and this results in the presence of large, and potentially immunogenic, peptides at the intestinal mucosa surface. During the last decade, several studies have defined gluten peptides able to stimulate adaptive T cells, of either CD4 or CD8 phenotype, and to activate innate (non T) immune cells. This review examines the complete repertoire of gluten peptides recognized by celiac T cells and discusses the several translational implications that the identification of these epitopes opens.

Can Consumers Trust Web-Based Information About Celiac Disease? Accuracy, Comprehensiveness, Transparency, and Readability of Information on the Internet

BackgroundCeliac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content.ObjectivesTo determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease.MethodsUsing the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality.ResultsWe included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of 98 (52%) websites contained less than 50% of the core celiac disease information that was considered important for inclusion on websites that provide general information about celiac disease. Academic websites were significantly less transparent (P = .005) than commercial websites in attributing authorship, timeliness of information, sources of information, and other important disclosures. The type of website publisher did not predict website accuracy, comprehensiveness, or overall website quality. Only 4 of 98 (4%) websites achieved an overall quality score of 80 or above, which a priori was set as the minimum score for a website to be judged trustworthy and reliable.ConclusionsThe information on many websites addressing celiac disease was not sufficiently accurate, comprehensive, and transparent, or presented at an appropriate reading grade level, to be considered sufficiently trustworthy and reliable for patients, health care providers, celiac disease support groups, and the general public. This has the potential to adversely affect decision making about important aspects of celiac disease, including its appropriate and proper diagnosis, treatment, and management.

Polymorphism of the storage proteins in Portuguese rye (Secale cereale L.) populations

Currently, due to the abandonment of traditional agricultural practices and the decline of rye production in Portugal, there is a need to assess the genetic diversity of rye in order to preserve its biodiversity. Furthermore, a greater knowledge of rye secalins is important for rye bread-making quality and other crop breeding purposes. The genetic variation and diversity of storage proteins were estimated for fourteen populations of rye (Secale cereale L.) sampled in northern Portugal. The work showed the high genetic diversity within the Portuguese rye gene-pool as an important source for plant breeding and emphasized the necessity of an integrated resources genetic program to allow a more efficient management and conservation of these resources. The rye populations were compared with 'Picasso' and 'Marder' varieties. Several alleles were identified by the single electrophoretic mobility patterns. We studied a set of 1600 rye seeds, including regional populations and varieties, having observed a total of 24, 5, 21 and 47 alleles for HMW, 75k γ-, 40k γ- and ω-secalins, respectively. The coefficient of similarity within populations is presented using cluster representation. The mean value of genetic variation indices (H) for rye storage proteins was very high in regional populations, ranging from 0.67 to 0.78, while in the varieties ranged from 0.57 to 0.58. Knowledge of the diversity of secalins will increase our understanding of the quality differences between rye varieties, especially considering the relative small number of rye cultivars grown around the world.

Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules.

Celiac disease is caused by an abnormal intestinal T-cell response to gluten proteins of wheat, barley and rye. Over the last few years, a number of gluten T-cell epitopes restricted by celiac disease associated HLA-DQ molecules have been characterized. In this work, we give an overview of these epitopes and suggest a comprehensive, new nomenclature.

Detergent-resistant Plasma Membrane Proteome in Oat and Rye: Similarities and Dissimilarities between Two Monocotyledonous Plants

The plasma membrane (PM) is involved in important cellular processes that determine the growth, development, differentiation, and environmental signal responses of plant cells. Some of these dynamic reactions occur in specific domains in the PM. In this study, we performed comparable nano-LC-MS/MS-based large-scale proteomic analysis of detergent-resistant membrane (DRM) fractions prepared from the PM of oat and rye. A number of proteins showed differential accumulation between the PM and DRM, and some proteins were only found in the DRM. Numerous proteins were identified as DRM proteins in oat (219 proteins) and rye (213 proteins), of which about half were identified only in the DRM. The DRM proteins were largely common to those found in dicotyledonous plants (Arabidopsis and tobacco), which suggests common functions associated with the DRM in plants. Combination of semiquantitative proteomic analysis and prediction of post-translational protein modification sites revealed differences in several proteins associated with the DRM in oat and rye. It is concluded that protein distribution in the DRM is unique from that in the PM, partly because of the physicochemical properties of the proteins, and the unique distribution of these proteins may define the functions of the specific domains in the PM in various physiological processes in plant cells.

Immune Development and Intestinal Microbiota in Celiac Disease

Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding), infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

Rheological properties and baking performance of rye dough as affected by transglutaminase

Since protein aggregation and formation of a continuous protein matrix in rye dough is very limited, an enzyme-induced protein aggregation method to improve the baking properties was investigated. The effects of microbial transglutaminase (TG) on the properties of rye dough were studied by rheological tests, confocal laser scanning microscopy (CSLM), standard-scale baking tests and crumb texture profile analysis. Addition of TG in the range of 0–4000 Ukg −1 rye flour modified the rheological properties of rye flour dough, resulting in a progressive increase of the complex shear modulus (| G∗|) and in a decrease of the loss factor (tan δ) due to protein cross-linking or aggregation. CLSM image analysis illustrated a TG-induced increase of the size of rye protein complexes. Standard baking tests showed positive effects on loaf volume and crumb texture of rye bread with TG applied up to 500 Ukg −1 rye flour. Higher levels of TG (500 U ≤ TG ≤ 4000 U) had detrimental effects on loaf volume. Increasing TG concentration resulted in an increase of crumb springiness and hardness. In conclusion, the results of this work demonstrated that TG can be used to improve the bread making performance of rye dough by creating a continuous protein network.

Immune-analytical detection of the cross-reactive major cereal allergens

Investigation of allergens of celiac disease and cereal allergy has become important for scientific research. Immune-blotting is currently one of the most appropriate methods applied for the identification of potential allergens. The research was focused on the examination of in vitro allergenic activity of proteins in domestic wheat, triticale, rye, barley, rice, corn, buckwheat and amaranth cultivars. The IgA/IgE reactive epitopes of water/salt- and alcohol-soluble protein fractions, respectively, were detected with IgA antibodies of celiac and IgE antibodies of wheat allergic human sera. Further efforts were made to separate the alpha-amylase inhibitors from the water/salt-soluble protein fraction of wheat by DEAE-cellulose anion-exchange chromatography and to confirm their presence on native gel. The most frequently recognised IgE reactive proteins (27) by wheat allergic human sera were identified by liquid chromatography coupled with mass spectroscopy and accession to databank supply. The pepsin resistance of identified wheat allergens was assessed directly on PVDF membrane-blotted protein bands.

Enzymatic Strategies to Detoxify Gluten: Implications for Celiac Disease

Celiac disease is a permanent intolerance to the gliadin fraction of wheat gluten and to similar barley and rye proteins that occurs in genetically susceptible subjects. After ingestion, degraded gluten proteins reach the small intestine and trigger an inappropriate T cell-mediated immune response, which can result in intestinal mucosal inflammation and extraintestinal manifestations. To date, no pharmacological treatment is available to gluten-intolerant patients, and a strict, life-long gluten-free diet is the only safe and efficient treatment available. Inevitably, this may produce considerable psychological, emotional, and economic stress. Therefore, the scientific community is very interested in establishing alternative or adjunctive treatments. Attractive and novel forms of therapy include strategies to eliminate detrimental gluten peptides from the celiac diet so that the immunogenic effect of the gluten epitopes can be neutralized, as well as strategies to block the gluten-induced inflammatory response. In the present paper, we review recent developments in the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten.

Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease.

Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4+ T cells play a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. Here we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T cell proliferation and inhibited pro-inflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin specific T cell clones obtained from patients with celiac disease. The results from our in vitro studies suggest that HLA-DQ2.5 derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T cell mediated inflammation and the associated production of proinflammatory cytokines.

Celiac disease: how complicated can it get?

In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4+ T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4+ T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma.

Evolutionary and Functional Analysis of Celiac Risk Loci Reveals SH2B3 as a Protective Factor against Bacterial Infection

Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (Fst) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.

Toxic, Immunostimulatory and Antagonist Gluten Peptides in Celiac Disease

Celiac disease (CD) is an increasingly diagnosed, permanent autoimmune enteropathy, triggered, in susceptible individuals, by the ingestion of gluten, the alcohol - soluble protein fraction of some cereals, such as wheat, rye and barley. The main protein of wheat gluten is called gliadin, the similar proteins of rye and barley are secalin and hordein, respectively. Approximately 96% of CD patients express the HLA molecule DQ2, while the remainder mostly express the less common haplotype DQ8, reflecting the pivotal role of these molecules in the pathogenesis of CD. Because of their aminoacid sequence and tri-dimensional structure, gluten peptides selectively bind to these HLA alleles present on the surface of antigen presenting cells and then they are presented to the T lymphocytes in intestinal mucosa, thus starting the inflammatory immune response. CD is defined by the characteristic histological changes of small bowel mucosa: villous atrophy, crypts hyperplasia and T cells infiltration of the lamina propria, along with the increase of the number of intra-epithelial lymphocytes. The withdrawal of the gluten- containing food from the diet determines a complete recovery of the intestinal mucosa, whereas the reintroduction causes a relapse of the disease. This review focuses on the description of gluten peptides that elicit the mucosal immune response via the activation of innate and adaptive immunity in CD. It also describes the antagonist gluten peptides, obtained by artificial modification of gluten T epitopes or naturally occurring in the alcohol protein fraction of a cultivar of durum wheat, able to immuno-modulate the pathogenic immune response of CD.

Dissecting Meiosis of Rye using Translational Proteomics

Much of our understanding of the genetic control of meiosis has come from recent studies of model organisms, which have given us valuable insights into processes such as recombination and the synapsis of chromosomes. The challenge now is to determine to what extent these models are representative of other groups of organisms, and to what extent generalisations can be made as to how meiosis works. Through a comparative proteomic approach with Arabidopsis thaliana, this study describes the spatial and temporal expression of key structural and recombinogenic proteins of cereal rye (Secale cereale). Antibodies to two synaptonemal complex-associated proteins (Asy1 and Zyp1) and two recombination-related proteins (Spo11 and Rad51) of A. thaliana were bound to meiocytes throughout meiotic prophase of rye, and visualized using conventional fluorescence microscopy and confocal laser scanning microscopy. Western analysis was performed on proteins extracted from pooled prophase I anthers, as a prelude to more advanced proteomic investigations. The four antibodies of A. thaliana reliably detected their epitopes in rye. The expression profile of Rad51 is consistent with its role in recombination. Asy1 protein is shown for the first time to cap the ends of bivalents. Western analysis reveals structural variants of the transverse filament protein Zyp1. Asy1 cores are assembled by elongation of early foci. The persistence of foci of Spo11 to late prophase does not fit the current model of molecular recombination. The putative structural variants of Zyp1 may indicate modification of the protein as bivalents are assembled.

Optimization of non-fermented gluten-free dough composition based on rheological behavior for industrial production of “empanadas” and pie-crusts

Celiac disease is an autoimmune disorder caused by intolerance to gluten, which is found in wheat and similar proteins in barley, rye and oats. The present study was designed to examine the effects of the addition of gums, whey protein concentrate, dry egg, and water to corn and cassava starches on the rheological properties of a non-fermented dough used for the production of “empanadas” (a traditional meal in Latin América) and pie-crusts suitable for people with celiac disease. A 2 4 full factorial design was chosen. Viscoelastic measurements and texture analysis (puncture and elongation tests) were performed. The increase in gums content and the decrease in water level produced an increase in both moduli ( G′ and G″) and a more elastic dough was obtained. Higher protein contents interfered with the formation of the three-dimensional gum network making the dough less ductile. Texture analysis led to similar conclusions to those obtained by dynamic rheological analysis. Formulations containing higher percentages of gums and lower water content led to an appropriate behavior for industrial production of these doughs.

Transamidation of Wheat Flour Inhibits the Response to Gliadin of Intestinal T Cells in Celiac Disease

Celiac disease is characterized by activation of HLA-DQ2/DQ8-restricted intestinal gluten-specific CD4(+) T cells. In particular, gluten becomes a better T-cell antigen following deamidation catalyzed by tissue transglutaminase. To date, the only available therapy is represented by adherence to a gluten-free diet. Here, we examined a new enzyme strategy to preventively abolish gluten activity. Enzyme modifications of the immunodominant alpha-gliadin peptide p56-68 were analyzed by mass spectrometry, and peptide binding to HLA-DQ2 was simulated by modeling studies. Wheat flour was treated with microbial transglutaminase and lysine methyl ester; gliadin was subsequently extracted, digested, and deamidated. Gliadin-specific intestinal T-cell lines (iTCLs) were generated from biopsy specimens from 12 adult patients with celiac disease and challenged in vitro with different antigen preparations. Tissue transglutaminase-mediated transamidation with lysine or lysine methyl ester of p56-68 or gliadin in alkaline conditions inhibited the interferon gamma expression in iTCLs; also, binding to DQ2 was reduced but not abolished, as suggested by in silico analysis. Lysine methyl ester was particularly effective in abrogating the activity of gliadin. Notably, a block in the response was observed when iTCLs were challenged with gliadin extracted from flour pretreated with microbial transglutaminase and lysine methyl ester. Transamidation of wheat flour with a food-grade enzyme and an appropriate amine donor can be used to block the T cell-mediated gliadin activity. Considering the crucial role of adaptive immunity in celiac disease, our findings highlight the potential of the proposed treatment to prevent cereal toxicity.

Celiac Disease Among Children and Adolescents

Celiac disease (CD) is a chronic disorder caused by an inflammatory T-cell response to the storage proteins in wheat (gliadin), rye (secalin), and barley (hordein), which are collectively called “gluten” and characterized by the presence of typical autoantibodies and histological alterations of the small bowel mucosa. Genetic, immunological, and environmental factors are necessary for the expression of the disease. Ingestion of gluten by genetically predisposed people precipitates an uncontrolled T-cell-driven inflammatory response that leads to disruption of the structural and functional integrity of the small bowel mucosa. CD is treated with a gluten-free diet (GFD), which leads to resolution of the clinical disease and restoration of the histological abnormalities. CD was once thought to be a rare condition, but at the present time it is accepted that CD is the most common form of food hypersensitivity in children and adults. The first description of CD is attributed to Aretaeus the Cappadocian, who lived in the second century AD. 1 He noted the characteristic stool and chronic nature of the condition and observed that children could also be affected by the disease. In 1888, Samuel Gee, a physician working at the St. Bartholomew Hospital in London, provided a thorough description of the clinical features of childhood CD. 2 During the first half of the past century, it was generally agreed that the treatment for CD was rest and diet. In 1924 Sidney Haas described his treatment of childhood CD with a banana diet, 3 but there was hardly any form of