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Background: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures., Objective: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard., Methods: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result., Results: Compared with SIC, sIgE levels of 0.35 kU A /L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kU A /L for wheat and to 6.20 kU A /L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE., Conclusion: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of T H 2 biomarkers., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Egg allergy is common and caused by sensitization to ovomucoid and/or ovalbumin. Many egg-allergic patients are able to tolerate eggs baked into other foods, such as muffins. Although heating egg extensively reduces allergens, the effect of other food ingredients on allergenicity of eggs, or the "matrix effect," is less well studied., Objective: We aimed to define how food matrices impact the matrix effect in egg allergenicity., Methods: Enzyme-linked immunosorbent assay was used to quantify ovalbumin and ovomucoid in extracts from various baked egg products: plain baked egg without a matrix, and muffins baked using either wheat flour, rice flour, or a wheat flour/banana puree mix. Allergen-specific immunoglobulin E (IgE)-blocking enzyme-linked immunosorbent assays were performed using the egg product extracts on egg-allergic patient sera to determine whether the amount of extracted egg protein in each extract correlated with how well the extracts could bind patients' egg IgE., Results: Baking eggs in any muffin matrix led to an increase in the amount of extractable ovalbumin and a decrease in the amount of extractable ovomucoid compared with plain baked egg. Compared with wheat muffins, rice muffins had more extractable ovalbumin and wheat/banana muffins had more extractable ovalbumin and ovomucoid. The egg allergens in the extracts were able to block egg-allergic patients' egg IgE., Conclusions: Food matrices affect egg allergen availability. Patients and families should be advised that substitutions in baked egg muffin recipes can affect the amount of egg allergens in foods and potentially affect the risk of food allergic reaction., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to report.

Background: Wheat allergy (WA), characterized by immunological responses to wheat proteins, is a gluten-related disorder that has become increasingly recognized in recent years. Bibliometrics involves the quantitative assessment of publications within a specific academic domain., Objectives: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy., Methods: We searched the Web of Science database on 5th Dec 2023. We used the keywords "wheat allergy or wheat anaphylaxis or wheat hypersensitivity," "gliadin allergy or gliadin anaphylaxis or gliadin hypersensitivity," "wheat-dependent exercise-induced anaphylaxis," and "baker's asthma" for our search. All items published between 1993 and 2023 were included. The top 100 most cited articles were identified and analyzed., Results: Our study conducted an in-depth bibliometric analysis of the 100 most-cited articles in the field of wheat allergy, published between 2002 and 2019. These articles originated from 20 different countries, predominantly Japan and Germany. The majority of these articles were centered on the pathogenesis and treatment of wheat allergy (WA). The Journal of Allergy and Clinical Immunology (JACI) was the most prolific contributor to this list, publishing 14 articles. The article with the highest citation count was published by Biomed Central (BMC) and garnered 748 citations. The peak citation year was 2015, with a total of 774 citations, while the years 1998, 2001, and 2005 saw the highest publication frequency, each with 7 articles., Conclusion: Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of wheat allergy, and help clinicians effectively obtain useful articles that have a significant impact on the field of wheat allergy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhan, Hou, Wen and Xu.)

Introduction: The association between food protein-induced enterocolitis syndrome (FPIES) and wheat ingestion in children with celiac disease is unknown at this time., Methods: We present seven cases of children with celiac disease who presented with symptoms of wheat-triggered acute FPIES (a-FPIES). An oral food challenge (OFC) with wheat allergen followed by 4 h of observation was performed. Activation of innate system cells was measured at baseline (T0), during symptoms (Ts), and 4 h after symptom onset (Ts + 4). A panel of human inflammatory cytokines was also performed., Results: All patients reacted to the first allergen dose. Three patients experienced a decrease of 30 mm Hg in systolic blood pressure and tachycardia and required hemodynamic resuscitation. Neutrophilia and a decrease in eosinophil count were evident at 4 h after symptom onset. At 4 h after symptom onset, cytokines (IL-6 and IL-8, and to a lesser degree, IL-10) were elevated., Conclusion: In a small sample of celiac patients with wheat exposure in an OFC, symptoms and acute immunological changes in serum inflammatory cytokine profile were consistent with a-FPIES., (© 2024 S. Karger AG, Basel.)

Competing Interests: Competing interests: None declared.

In recent years, the prevalence of allergic diseases has increased significantly, causing great concern, and wheat, as one of the top 8 food allergens, is a common allergy trigger. Nevertheless, reliable estimates of the positivity rate of wheat allergens in the allergic population in China are still lacking. The systematic review and meta-analysis aims to evaluate the positive detection rate of wheat allergens in the Chinese allergic population and further provide a reference for the prevention of allergy. CNKI, CQVIP, WAN-FANG DATA, Sino Med, PubMed, Web of Science, Cochrane Library, and Embase databases were retrieved. Related research and case reports about the positive rate of wheat allergen in the Chinese allergic population published from inception to June 30, 2022, were searched, and meta-analysis was performed using Stata software. The pooled positive rate of wheat allergens and 95% confidence interval were calculated by random effect models, and the publication bias was evaluated using Egger's test. A total of 13 articles were included for the final meta-analysis, in which wheat allergen detection methods involved only serum sIgE testing and SPT assessment. The results showed that the wheat allergen positivity detection rate in Chinese allergic patients was 7.30% (95% CI 5.68-8.92%). Subgroup analysis showed that the positivity rate of wheat allergens was influenced by region, but hardly by age and assessment method. The positive rates of wheat allergy in the population with allergic diseases were 2.74% (95% CI 0.90-4.58%) and 11.47% (95% CI 7.08-15.87%) in southern and northern China, respectively. In particular, the positive rates of wheat allergens were greater than 10% in Shaanxi, Henan and Nei Mongol, all of which belong to the northern region. These results suggest that wheat allergens are an important cause of sensitization in allergic populations from northern China, and therefore attention should be paid to early prevention in high-risk populations., (© 2023. The Author(s).)

Objective: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet., Research Design and Methods: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage., Results: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis., Conclusions: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction., (© 2022 by the American Diabetes Association.)

Introduction: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated., Methods: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT)., Results: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022)., Conclusion: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision., (© 2021 S. Karger AG, Basel.)

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence. We evaluated the potential synergistic effects that peptic-tryptic-digested gliadin (PT) and the most-used food mNPs may induce on the intestinal mucosa. PT interaction with mNPs and their consequent aggregation was detected by transmission electron microscopy (TEM) analyses and UV-Vis spectra. In vitro experiments on Caco-2 cells proved the synergistic cytotoxic effect of PT and mNPs, as well as alterations in the monolayer integrity and tight junction proteins. Exposure of duodenal biopsies to gliadin plus mNPs triggered cytokine production, but only in CeD biopsies. These results suggest that mNPs used in the food sector may alter intestinal homeostasis, thus representing an additional environmental risk factor for the development of CeD.

Previous researchers have shown the potential of sourdough and isolated lactic acid bacteria in reducing wheat allergens. As the interactions of lactic acid bacteria with yeast is a key event in sourdough fermentation, we wished to investigate how yeast affects metabolism of lactic acid bacteria, thereby affecting protein degradation and antigenic response. In this study, three strains isolated from sourdough were selected for dough fermentation, namely Pediococcus acidilactici XZ31, Saccharomyces cerevisiae JM1 and Torulaspora delbrueckii JM4. The changes in dough protein during the fermentation process were studied. Protein degradation and antigenic response in dough inoculated with Pediococcus acidilactici XZ31 monoculture and co-culture with yeast were mainly evaluated by SDS-PAGE, immunoblotting, ELISA and Liquid chromatography-tandem mass spectrometry assay. The whole-genome transcriptomic changes in Pediococcus acidilactici XZ31 were also investigated by RNA sequencing. The results showed that water/salt soluble protein and Tri a 28/19 allergens content significantly decreased after 24 h fermentation. Co-culture fermentation accelerated the degradation of protein, and reduced the allergen content to a greater extent. RNA-sequencing analysis further demonstrated that the presence of yeast could promote protein metabolism in Pediococcus acidilactici XZ31 for a certain period of time. These results revealed a synergistic effect between Pediococcus acidilactici XZ31 and yeast degrading wheat allergens, and suggested the potential use of the multi-strain leavening agent for producing hypoallergenic wheat products., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction and Objectives: Wheat and cereal grains have a broad range of cross-reactivity, but the clinical relevance of this cross-reactivity is uncertain. This study aimed to evaluate clinical and in vitro cross-reactivity with barley, oat, and Job's tears among wheat-allergic patients., Materials and Methods: Patients aged 5 to 15 years with IgE-mediated wheat allergy were enrolled. Skin prick test (SPT) and specific IgE (sIgE) to wheat, barley, and oat, and SPT to Job's tears were performed. Oral food challenge (OFC) was conducted if the SPT was ≤5 mm in size and there was no history of anaphylaxis to each grain. Profiles of sIgE bound allergens of wheat, barley, and oat, and inhibition ELISA of IgE binding to barley and oat with wheat were performed., Results: Ten patients with a median age of 8 years were enrolled. Nine of those patients had a history of wheat anaphylaxis. The median SPT size and sIgE level to wheat was 7.3 mm and 146.5 kU A /l, respectively. The cross-reactivity rate for barley, oat, and Job's tears was 60.0%, 33.3%, and 20.0%, respectively. Significantly larger SPT size and higher sIgE level were observed in patients with positive cross-reactivity to barley and oat when compared to patients without cross-reactivity. Barley and oat extracts inhibited 59% and 16% of sIgE bound to wheat gliadins and glutenins, respectively., Conclusion: The cross-reactivity rate was quite low for oat and Job's tears compared to that of barley; therefore, avoidance of all cereal grains may be unnecessary in patients with severe wheat allergy., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been associated with both dyspeptic symptoms and duodenal eosinophilia, suggesting an overlap between these two conditions. The aim of this study was to evaluate the role of wheat (specifically gluten and fructans) in symptom reduction in participants with FD in a pilot randomized double-blind, placebo controlled, dietary crossover trial. Methods: Patients with Rome III criteria FD were recruited from a single tertiary centre in Newcastle, Australia. All were individually counselled on a diet low in both gluten and fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) by a clinical dietitian, which was followed for four weeks (elimination diet phase). Those who had a >30% response to the run-in diet, as measured by the Nepean Dyspepsia Index, were then re-challenged with 'muesli' bars containing either gluten, fructan, or placebo in randomised order. Those with symptoms which significantly reduced during the elimination diet, but reliably reappeared (a mean change in overall dyspeptic symptoms of >30%) with gluten or fructan re-challenge were deemed to have wheat induced FD. Results: Eleven participants were enrolled in the study (75% female, mean age 43 years). Of the initial cohort, nine participants completed the elimination diet phase of whom four qualified for the rechallenge phase. The gluten-free, low FODMAP diet led to an overall (albeit non-significant) improvement in symptoms of functional dyspepsia in the diet elimination phase (mean NDI symptom score 71.2 vs. 47.1, p = 0.087). A specific food trigger could not be reliably demonstrated. Conclusions: Although a gluten-free, low-FODMAP diet led to a modest overall reduction in symptoms in this cohort of FD patients, a specific trigger could not be identified. The modified Salerno criteria for NCG/WS identification trialled in this dietary rechallenge protocol was fit-for-purpose. However, larger trials are required to determine whether particular components of wheat induce symptoms in functional dyspepsia., Competing Interests: Kerith Duncanson is a company director for the Good Gut Group, that has patented functional bread and grain product concepts (Australian Patent No. 2014262285; New Zealand Patent No. 629207; South Africa Patent No. 2015/07891) for Irritable Bowel Syndrome (IBS) consumers. Good Gut Group had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Natural tolerance in hexaploid bread wheat (Triticum aestivum L.) to synthetic auxin herbicides is primarily due to rapid metabolic detoxification, but genes encoding these herbicide-detoxifying enzymes have yet to be identified. Herbicide safeners are commonly applied in wheat to achieve herbicide tolerance by inducing the expression and activity of herbicide-detoxifying enzymes. While safeners have been utilized for decades, knowledge of mechanisms that induce gene expression is limited. Our objective was to identify wheat chromosomes possessing genes that endow natural or safener-induced tolerance to halauxifen-methyl (HM), a postemergence (POST) wheat-selective synthetic auxin herbicide, using alien substitution (the S genome of Aegilops searsii) and aneuploid lines. Two POST rates of HM were applied to seedlings with 1-2 leaves (Zadoks stages 11-12), and the highest HM rate was also applied with the safener cloquintocet-mexyl (CM). Wheat chromosomes possessing genes associated only with natural HM tolerance were identified because Ae. searsii is HM-sensitive but CM-responsive. Lines with substitutions for 5A and 5B displayed sensitivity to HM, and experiments with nullisomic-tetrasomic (NT) lines further indicated major genes associated with HM tolerance are present on 5A and 5B chromosomes. However, the genes on 5A appear to play a larger role because lines lacking 5A chromosomes displayed more sensitivity than lines lacking 5B. Overall, these results can be utilized to guide future transcriptome analyses to identify candidate genes that confer HM tolerance in wheat.

Background: Oral immunotherapy (OIT) use in patients with wheat anaphylaxis is not well studied. We assessed the efficacy of low-dose OIT for patients with wheat-induced anaphylaxis., Methods: Eligible subjects were aged 5-18 years with a history of wheat anaphylaxis and confirmed symptoms during oral food challenge (OFC) to 53 mg of wheat protein. After admission to the hospital for a 5-day buildup phase, patients in the OIT group gradually increased wheat ingestion to 53 mg/day and then ingested 53 mg daily at home. One year later, they underwent 53- and 400-mg OFCs after OIT cessation for 2 weeks. The historical control group was defined as patients who avoided wheat during the same period., Results: Median wheat- and ω-5 gliadin-specific immunoglobulin E (sIgE) levels were 293 and 7.5 kU A /L, respectively, in the OIT group (16 children). No patients dropped out. Within 1 year, 88% of patients in the OIT group reached 53 mg. After 1 year, 69% and 9% patients passed the 53-mg OFC and 25% and 0% passed the 400-mg OFC in the OIT and control groups (11 children), respectively (P = .002 and 0.07, respectively). In the OIT group, wheat- and ω-5 gliadin-sIgE levels significantly decreased to 154 and 4.1 kU A /L, respectively, at 1 year, and wheat- and ω-5 gliadin-specific IgG and IgG 4 levels significantly increased at 1 month. Anaphylaxis developed 7 times and promptly improved without adrenaline., Conclusion: For patients with wheat anaphylaxis, low-dose OIT safely induces immunologic changes, achieves low-dose desensitization, and may allow for a 400 mg dose., (© 2020 John Wiley & Sons A/S Published by John Wiley and Sons Ltd.)

Background : Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods : A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results : Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions : The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms.

We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune responses in NCWS/FMF patients challenged with wheat vs. rice. The study was conducted at the Department of Internal Medicine of the University Hospital of Palermo and the Hospital of Sciacca, Italy. Six female volunteers with FMF/NCWS (mean age 36 ± 6 years) were enrolled, 12 age-matched non-FMF, NCWS females, and 8 sex- and age-matched healthy subjects served as controls. We evaluated: 1. clinical symptoms by the FMF-specific AIDAI (Auto-Inflammatory Diseases Activity Index) score; 2. serum soluble CD14 (sCD14), C-reactive protein (CRP), and serum amyloid A (SSA); 3. circulating CD14 + monocytes expressing interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The AIDAI score significantly increased in FMF patients during DBPC with wheat, but not with rice (19 ± 6.3 vs. 7 ± 1.6; p = 0.028). sCD14 values did not differ in FMF patients before and after the challenge, but were higher in FMF patients than in healthy controls (median values 11357 vs. 8710 pg/ml; p = 0.002). The percentage of circulating CD14 + /IL-1β + and of CD14 + /TNF-α + monocytes increased significantly after DBPC with wheat vs. baseline or rice challenge. Self-reported NCWS can hide an FMF diagnosis. Wheat ingestion exacerbated clinical and immunological features of FMF. Future studies performed on consecutive FMF patients recruited in centers for auto-inflammatory diseases will determine the real frequency and relevance of this association.

A subchronic toxicity study were conducted in Wistar Han RCC rats to evaluate the potential health effects of genetically modified (GM), drought-tolerant wheat MGX11-10. Rats were fed a rodent diet formulated with MGX11-10 and were compared with rats fed a diet formulated with its corresponding non-transgenic control Jimai22 and rats fed a basal diet. MGX11-10 and Jimai22 were ground into flour and formulated into diets at concentrations of 16.25, 32.5, or 65%, w/w% and fed to rats (10/sex/group) for 13 weeks. Compared with rats fed Jimai22 and the basal-diet group, no biologically relevant differences were observed in rats fed the GM diet with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, clinical chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, the MGX11-10 diets did not cause any treatment-related effects in rats following at least 90 days of dietary administration as compared with rats fed diets with the corresponding non-transgenic control diet and the basal-diet group. The MGX11-10 diets are considered equivalent to the diets prepared from conventional comparators. The results demonstrated that MGX11-10 wheat is as safe and wholesome as the corresponding non-transgenic control wheat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe allergic condition in which wheat ingestion together followed by physical exercise induces anaphylaxis. For patients with WDEIA, omega-5 gliadin is considered to be one of the major allergens., Aim: To analyse the clinical features and allergen spectrum of WDEIA and to investigate the relationship between WDEIA and serum levels of platelet-activating factor (PAF), interleukin (IL)-9 and IL-33., Methods: Medical histories and conditions of WDEIA cases were collected and summarized, with allergen tests of wheat proteins measured at the same visit. Of the 33 patients enrolled, 13 also had serum levels of PAF, IL-9 and IL-33 measured. The healthy control (HC) group consisted of 13 healthy individuals, who also underwent both the wheat-protein allergen tests and the inflammatory-mediator tests., Results: All patients experienced severe allergic reaction during exercise after wheat ingestion. Manifestations of WDEIA included facial oedema, generalized urticaria and respiratory symptoms. Unconsciousness was also observed in 21 cases. In the patient group, 57.6% were confirmed as hypersensitive to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), while 54.5% were allergic to omega-5 gliadin. PAF concentration was significantly higher in patients with WDEIA compared with HCs, whereas there was no significant difference in IL-9 or IL-33 between the two groups., Conclusions: WDEIA is a rare type of anaphylaxis. GAPDH and omega-5 gliadin may be the most common allergy-causing wheat proteins for Chinese people. PAF may be associated with the onset and development of WDEIA., (© 2019 British Association of Dermatologists.)

Wheat is a common cereal in the Western diet and an important source of protein as well as fiber. However, some individuals develop adverse reactions to a wheat-containing diet. The best characterized is celiac disease which develops after intake of gluten in individuals with genetic predisposition. Other wheat-related conditions are less well defined in terms of diagnosis, specific trigger and underlying pathways. Despite this, the overall prevalence of wheat-related disorders has increased in the last decades and the role of microbial factors has been suggested. Several studies have described an altered intestinal microbiota in celiac patients compared to healthy subjects, but less information is available regarding other wheat-related disorders. Here, we discuss the importance of the intestinal microbiota in the metabolism of wheat proteins and the development of inflammatory or functional conditions. Understanding these interactions will open new directions for therapeutic development using bacteria with optimal wheat protein degrading capacity., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Gluten-related disorders are very common in pediatric patients. Wheat allergy is triggered by an immunoglobulin E (IgE)-dependent mechanism; its prevalence varies according to the age and region, and in Europe has been estimated to be lower than 1%. Many studies investigated the potential role of several external factors that can influence the risk to developing wheat allergy, but results are still inconclusive. It can be responsible for several clinical manifestations depending on the route of allergen exposure: food-dependent exercise-induced anaphylaxis (FDEIA), occupational rhinitis or asthma (also known as baker's asthma), and contact urticaria. The prognosis of IgE-mediated wheat allergy in children is generally favorable, with the majority of children becoming tolerant by school age. Patients who experienced an anaphylactic reaction prior to 3 years of age and patients with higher level of wheat- or ω-5 gliadin-specific IgE antibodies seem to be at higher risk of persistent wheat allergy. The current management of patients is dietary avoidance. Nowadays, oral immunotherapy has been proposed for wheat allergy with promising results, even if further studies are necessary to establish the best protocol in order to promote tolerance in wheat-allergic children., Competing Interests: The authors declare no conflict of interest.

Background & Aims: Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial., Methods: C57BL/6 (control), Myd88 -/- , Ticam1 -/- , and Il15 -/- mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and intestinal transit. Control mice fed ATIs for 1 week were gavaged daily with Lactobacillus strains that had high or low ATI-degrading capacity. Nonobese diabetic/DQ8 mice were sensitized to gluten and fed an ATI diet, a gluten-containing diet or a diet with ATIs and gluten for 2 weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. Intestinal tissues were collected and IELs, gene expression, gut permeability and intestinal microbiota profiles were measured., Results: In intestinal tissues from control mice, ATIs induced an innate immune response by activation of Toll-like receptor 4 signaling to MD2 and CD14, and caused barrier dysfunction in the absence of mucosal damage. Administration of ATIs to gluten-sensitized mice expressing HLA-DQ8 increased intestinal inflammation in response to gluten in the diet. We found ATIs to be degraded by Lactobacillus, which reduced the inflammatory effects of ATIs., Conclusions: ATIs mediate wheat-induced intestinal dysfunction in wild-type mice and exacerbate inflammation to gluten in susceptible mice. Microbiome-modulating strategies, such as administration of bacteria with ATI-degrading capacity, may be effective in patients with wheat-sensitive disorders., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Wheat-related disorders are a spectrum of disorders associated with different autoimmune and non-autoimmune diseases. However, it is unclear whether these wheat-related disorders lead to adverse health effects such as cardiovascular risk, nutritional deficiencies etc. The objective of the study was to explore the lipid profiles and the nutritional status of subjects with wheat-related disorders to understand the potential threat of wheat on cardiovascular risk and nutritional deficiency. Method: A total of 1041 subjects who showed wheat-related symptoms were initially tested for the wheat protein antibody panel (Wheat Zoomer (WZ) panel and Coeliac Disease (CD) panel), then for cardiovascular panel and the micronutrient panel at Vibrant America Clinical Laboratory. Results: Subjects with both Wheat Zoomer positivity (WZ+) and Coeliac Disease positivity (CD+) had significantly low levels of high-density lipoproteins (HDL) (279/483(57.8%) and 29/47(61.7%) respectively), but only subjects with WZ + had low levels of Apo A1 (44/424(9.5%)), and high levels of Omega 6 fatty acids (53/334(15.9%)). None of the micronutrients tested showed a significant imbalance in WZ + subjects. Conclusion: Subjects with positive serology for WZ have deranged blood lipid profiles but did not show any significant micronutrient deficiency. Hence, our results showcase a significant association of wheat-related disorders to cardiovascular risk.

Purpose of Review: There has been significant interest in gluten over the last decade, with an increase in interest of gluten-related disorders outside coeliac disease. Particularly, there has been a focus on the role of gluten in noncoeliac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS). There is significant overlap between both of these conditions, with the aim of this review to explore their complex relationship., Recent Findings: Gluten has been demonstrated to generate symptoms in individuals with NCGS. However, there appears to be an increasing role for gluten in symptom generation in patients with IBS also. Other components of wheat, other than gluten, are now also thought to be contributing factors in symptom generation., Summary: There appears to be significant overlap between IBS and NCGS. It is likely that a subset of patients presenting with IBS actually have NCGS. In addition, it is likely that individuals with IBS may also have symptoms triggered by gluten. With the pathophysiology of both conditions not fully understood, as well as increasing knowledge of wheat components in symptom generation, further research is required to help distinguish between both.

Background and Objective: Wheat ingestion can lead to disorders such as IgE-mediated food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA), both of which are associated with impaired quality of life and significant morbidity. Allergy to wheat is relatively benign in children, although its natural history in adults is still unknown. Objective: We used placebo-controlled challenge to evaluate the natural history of wheat hypersensitivity in atopic patients with adultonset wheat allergy., Methods: We enrolled 13 patients from an initial cohort of adult patients with IgE-mediated wheat allergy (mean age, 40 years). After diagnosis, the patients observed a wheat-free diet and were followed as outpatients for 5 years to evaluate wheat exposure. Wheat-IgEtiters were determined at the end of follow-up, and a second wheat-challenge was performed., Results: Ten out of 13 patients took part in the study. The mean period of wheat avoidance was 4.2 years. Three patients had spontaneously reintroduced wheat before the second evaluation, after a mean (IQR) of 28 (18-36) months, with only mild gastrointestinal discomfort at reintroduction. At the end of follow-up, 9 of the 10 patients were wheat-tolerant. Two patients had a history of WDEIA. We observed a reduction in IgE levels, with median (IQR) IgE falling from 2.77 (0.35-100) kU/L at diagnosis to 0.88 (0.1-20.8) kU/L. The association between IgE and a negative challenge result was not statistically significant., Conclusion: IgE-mediated wheat allergy in adults is benign and represents a temporary break in gastrointestinal tolerance. Future studies may improve our knowledge of wheat allergens, routes of and factors leading to sensitization, and prognostic biomarkers.

The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

Gliadin, a component of wheat gluten known to be an important factor in the etiology of celiac disease, is related to several other diseases through its enhancing effect on intestinal paracellular permeability. We investigated the significance of gliadin in non-steroidal anti-inflammatory drug (NSAID)-induced small-intestinal damage in mice. 7-week-old C57BL/6 male mice were divided into the following groups: standard diet group, in which mice were fed with wheat-containing standard rodent diet (CE-2); gluten-free diet group, in which mice were fed with gluten-free diet (AIN-76A); and gliadin-administered group, in which mice fed with gluten-free diet were administered with gliadin (~250 mg/kg BW). Each group was subdivided into negative, healthy control group and NSAID-treated group. To some mice fed with gluten-free diet and administered with gliadin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was administered for clarification of the significance of EGFR in NSAID-induced small intestinal damage and intestinal permeability. In mice fed with a gluten-free diet, indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheat-containing standard diet. Gliadin exacerbated the NSAID-induced small-intestinal damage in mice fed with a gluten-free diet. With the administration of indomethacin, MPO activity, a marker of neutrophil infiltration into the mucosa and mRNA expression level of tumor necrosis factor α and interleukin-1β in the small intestine were higher in the gliadin-administered mice. Gliadin increased the intestinal paracellular permeability without indomethacin administration (4.3-fold) and further increased the permeability after indomethacin administration (2.1-fold). Gliadin induced phosphorylation of epidermal growth factor receptor (EGFR) in small-intestinal tissues, and erlotinib (an EGFR tyrosine kinase inhibitor) attenuated the indomethacin-induced intestinal damage and permeability exacerbated by gliadin, accompanied by inhibition of EGFR phosphorylation. These results suggest that gliadin plays an important role in the induction and exacerbation of NSAID-induced small-intestinal damage, and that increase in intestinal permeability via the EGFR signalling pathway is involved in its mechanism., Competing Interests: The authors have declared that no competing interests exist.

Coeliac disease is an immune-mediated enteropathy against dietary gluten present in wheat, rye and barley and is one of the most common lifelong food-related disorders worldwide. Coeliac disease is also considered to be a systemic disorder characterized by a variable combination of gluten-related signs and symptoms and disease-specific antibodies in addition to enteropathy. The ingestion of gluten leads to the generation of harmful gluten peptides, which, in predisposed individuals, can induce adaptive and innate immune responses. The clinical presentation is extremely variable; patients may have severe gastrointestinal symptoms and malabsorption, extraintestinal symptoms or have no symptoms at all. Owing to the multifaceted clinical presentation, diagnosis remains a challenge and coeliac disease is heavily underdiagnosed. The diagnosis of coeliac disease is achieved by combining coeliac disease serology and small intestinal mucosal histology during a gluten-containing diet. Currently, the only effective treatment for coeliac disease is a lifelong strict gluten-free diet; however, the diet is restrictive and gluten is difficult to avoid. Optimizing diagnosis and care in coeliac disease requires continuous research and education of both patients and health-care professionals.

Beer is one of the most consumed alcoholic beverages worldwide but allergic reactions to this beverage are uncommon. The authors present a case report of a 32-year-old male patient, sent to our Allergy and Immunology Department due to anaphylaxis minutes after Franziskaner beer ingestion. He tolerates all other alcoholic beverages. Prick tests to cereals were positive to wheat, corn and barley, as well as to peach. Prick-to-prick tests were performed with nine beer brands, all positive. Immunoglobulin (Ig)E to Pru p 3 was 14.8 kU/L. Sodium dodecyl sulfate polyacrylamide gel electrophoresis inhibition immunoblotting was performed with the Franziskaner beer extract in solid phase and both cereal extracts (wheat, barley and corn) and Pru p 3 as inhibitors. Extracts from wheat, barley and corn, and Pru p 3 purified protein were able to inhibit almost totally the IgE-binding to the Franziskaner beer extract. It seemed likely that the IgE-binding bands detected in the Franziskaner beer extract could be an LTP from cereals., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Germination is already a well-accepted process by consumers with many products made from sprouted seeds or containing limited amounts of flour form sprouted grains. The present work aimed assessing the usefulness of germination in reducing gluten peptides associated with celiac disease, at the same time evaluating some technological features of the obtained germinated wheat. In the first part of the work, celiac disease (CD)-triggering peptides were tracked as a function of germination kinetics (from day 1 to day 6). Using simulated gastrointestinal digestion and liquid chromatography coupled to mass spectrometry, ten celiac disease triggering peptides were identified: seven peptides presumably involved in the adaptive immune response (TI) and three peptides mainly involved in the innate immune response (TT). All the identified peptides belonged to gliadins. TI track pattern showed three phases: the first two days displayed a significant degradation, a stability phase was observed from day 3 to day 5, and finally a drastic reduction occurred on the 6th day. For TT peptides, important degradation was exclusively observed at the 6th day. In the second part, some techno-functional features of germinated whole wheat flour were assessed to estimate its potential as an alternative to conventional flour. Functionality comparison of the non-germinated versus germinated flours revealed that germination significantly influenced solvents retention capacities as well as swelling and solubility. Thus, with a reduced amount of celiac disease triggering peptides, but also with different technological behavior compared to traditional wheat flour., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aims: Diet appears to play a pivotal role in symptom generation in Irritable Bowel Syndrome (IBS). First line dietary therapy for IBS has focused on advice concerning healthy eating and lifestyle management. Research recently has focused on the role of a diet low in fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs), gluten free (GFD) and wheat free (WFD) diets for the relief of symptoms in IBS., Methods: A round table discussion with gastroenterologists and dietitians with a specialist interest in dietary therapies in IBS was held in Sheffield, United Kingdom in May 2017. Existing literature was reviewed. PubMed and EMBASE were searched with the MeSH terms irritable bowel syndrome/diet/diet therapy/gluten/low FODMAP in different combinations to identify relevant articles. A consensus on the application of these dietary therapies into day-to-day practice was developed., Results: Fourteen randomized trials in IBS evaluating the low FODMAP diet (n studies = 9), GFD (n = 4) and WFD (n = 1) were included in this review. The total number of patients recruited from randomized trials reviewed was: n=580 low FODMAP diet (female, n=430), n=203 GFD (female, n=139), n=276 WFD (female, n=215). There was no significant difference in the gender of patients recruited for both the low FODMAP and GFD randomized studies (p=0.12). The response rate in the literature to a low FODMAP diet ranged between 50-76%, and to GFD ranged between 34-71%. Percentage of IBS patients identified as wheat sensitive was reported as 30% in the literature., Conclusion: There are no head-to-head trials to date utilizing the low FODMAP diet, GFD and WFD for dietary treatment of IBS and still a number of concerns for diets, including nutritional inadequacy and alteration of the gut microbiota. The consensus suggests that there is evidence for the use of the low FODMAP diet, GFD and WFD as dietary therapies for IBS; the decision-making process for using each individual therapy should be directed by a detailed history by the dietitian, involving the patient in the process.

Purpose: The aim of this study was to understand the differential acute effects of two distinct wheat-related dusts, such as field or stored wheat dust handling, on workers' health and how those effects evolved at 6 month intervals., Methods: Exposure, work-related symptoms, changes in lung function, and blood samples of 81 workers handling wheat and 61 controls were collected during the high exposure season and 6 months after. Specific IgG, IgE, and precipitins against 12 fungi isolated from wheat dust were titrated by enzyme-linked immunosorbent assay, dissociation-enhanced lanthanide fluorescence immunoassay, and electrosyneresis. The level of fungi was determined in the workers' environment. Levels of exhaled fraction of nitrogen monoxide (F E NO) and total IgE were obtained. Exposure response associations were investigated by mixed logistic and linear regression models., Results: The recent exposure to field wheat dust was associated with a higher prevalence for five of six self-reported airway symptoms and with a lower F E NO than those in the control population. Exposure to stored wheat dust was only associated with cough. No acute impact of exposure on respiratory function was observed. Exposure to field wheat dust led to workers' sensitization against the three field fungi Aureobasidum, Cryptococcus, and Phoma, although exposure to storage wheat dust was associated with tolerance. The level of Ig remained stable 6 months after exposure., Conclusion: The clinical picture of workers exposed to field or storage wheat dust differed. The systematic characterization of the aerosol microbial profile may help to understand the reasons for those differences.

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South-East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Celiac disease (CD) and non-gluten (or wheat) sensitivity (NCGS) are two gluten-related disorders, the treatment of which relies on dietary withdrawal of gluten (absolute and lifelong in the case of CD patients). However, these conditions differ in their pathophysiology and impact on health. CD is an autoimmune disorder of the intestine, and is associated with a wide range of disorders, pre- and post-diagnosis. Its autoimmune and inflammatory nature raises concerns about its potential effects on mortality and morbidity. Here we review the data on the health impact CD or NCGS may have prospectively, and report on the role of a gluten-free diet (GFD) in this respect. Since study designs have been heterogeneous, we focus on studies of treated patients with a biopsy-proven diagnosis of CD, to eliminate possible bias from misdiagnosis. The review revealed a moderately increased mortality risk among CD patients, mainly attributed to cardiovascular disease and malignancy. Other long-term morbidities of CD include autoimmune disorders, nutritional deficiencies, impaired bone health, reproductive abnormalities, and neurologic and neuropsychiatric disorders, which are substantially improved, and some of them even completely treated, after strict adherence to a GFD. For NCGS, the literature is too limited and its long-term complications are unknown., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the ingestion of gluten-containing grains leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet, and it is diagnosed when celiac disease (CD) and wheat allergy (WA) have been ruled out. The limited knowledge about the pathophysiology of NCGS and the lack of validated biomarkers are still major limitations for clinical studies, making it difficult to differentiate NCGS from other gluten-related disorders (GRD). In the absence of clear-cut diagnostic criteria, NCGS is still mainly a diagnosis of exclusion. Several studies suggest that NCGS is an immune-mediated disease that likely activates an innate immune response. Moreover, it has recently been hypothesized that in addition to gluten, other components of wheat may be responsible for the symptoms observed in individuals without CD. This review aims at discussing available evidence related to the histological and immunological features in the gut mucosa of patients with NCGS and at outlining new dietary opportunities for these patients., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nonceliac gluten sensitivity (NCGS) is a gluten-related gastrointestinal disorder distinct from celiac disease (CD) and gluten allergy that is not easy to diagnose due to the lack of biomarkers. It is characterized by intestinal symptoms and extraintestinal manifestations with the consumption of gluten-containing foods. In contrast to CD, NCGS patients do not present a genetic predisposition or intestinal villi atrophy. Recent studies question the proinflammatory triggering activity of α-gliadin fraction contained in wheat, since it has been demonstrated that the amylase-trypsin inhibitors (ATIs) exert a strong activating effect on the innate immune response. We aimed to analyze the role of ATIs in the activation of innate immunity and in the development of the symptoms characteristic of NCGS. A systematic literature search was made using databases such as MEDLINE, SciELO, Science Direct, and Scopus, with focus on key words such as "amylase-trypsin inhibitors," "wheat," "gluten," and "celiac." Many studies are available on the structure, inhibition mechanism, and immune system effects of ATIs, mainly focused on IgE-mediated reactions. Recently, with the increase of NCGS interest, has increased the literature on the capacity of ATIs contained in wheat to activate the innate immune system. Literature published to date questions the relationship between activation of the innate immune system and gluten in NCGS. ATIs may have acted as interfering contaminant of gluten and appear as potential activator of innate immunity in NCGS patients. In view of their potential impact, more interventional studies are needed to demonstrate the proinflammatory effect of ATIs.

Objective: This study sought to understand how the dietary source of carbohydrates, either high-fructose corn syrup (HFCS) or complex carbohydrates, affects energy expenditure (EE) measures, appetitive sensations, and hormones during 24 hours of overfeeding., Methods: Seventeen healthy participants with normal glucose regulation had 24-hour EE measures and fasting blood and 24-hour urine collection during four different 1-day diets, including an energy-balanced diet, fasting, and two 75% carbohydrate diets (5% fat) given at 200% of energy requirements with either HFCS or whole-wheat foods as the carbohydrate source. In eight volunteers, hunger was assessed with visual analog scales the morning after the diets., Results: Compared with energy balance, 24-hour EE increased 12.8% ± 6.9% with carbohydrate overfeeding (P < 0.0001). No differences in 24-hour EE or macronutrient utilization were observed between the two high-carbohydrate diets; however, sleeping metabolic rate was higher after the HFCS diet (Δ = 35 ± 48 kcal [146 ± 200 kJ]; P = 0.01). Insulin, ghrelin, and triglycerides increased the morning after both overfeeding diets. Urinary cortisol concentrations (82.8 ± 35.9 vs. 107.6 ± 46.9 nmol/24 h; P = 0.01) and morning-after hunger scores (Δ = 2.4 ± 2.0 cm; P = 0.01) were higher with HFCS overfeeding., Conclusions: The dietary carbohydrate source while overeating did not affect 24-hour EE, but HFCS overconsumption may predispose individuals to further overeating due to increased glucocorticoid release and increased hunger the following morning., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

In this work, the aim is to study the effectiveness of germination on wheat protein degradation, with a specific focus on proteins involved in adverse reactions to wheat. The effects of 8 days of germination at 25 °C on the chemical composition and the protein profile were determined. Germination did not have a significant effect on starch, protein, lipid, and ash contents. General protein profile, as indicated by SDS-PAGE analysis, revealed that germination induced a relevant degradation in protein fraction. After in vitro gastrointestinal digestion, gluten peptides involved in celiac disease (CD) were identified and quantified using UPLC/ESI-MS technique. Also, CM3 protein, involved in baker's asthma and intestinal inflammation, was quantified by measuring a marker peptide. Statistical analysis underlined that germination and genotype had significant impact on the amount of both components. Regarding gluten peptides related to CD, germination enabled an average reduction of 47% in peptides eliciting adaptive immune response and 46% in peptides eliciting innate immune response. CM3 protein showed also a high average reduction (56%). Thus, this study suggests that germination might be a good bioalternative to provide a low "impact" raw ingredient for special wheat-based foodstuffs.