Wheat Challenge Research Articles

Fecal calprotectin levels in patients with non-celiac wheat sensitivity: a proof of concept

Some data suggest the existence of intestinal inflammation in patients with non-celiac wheat sensitivity (NCWS). We aimed to verify whether fecal calprotectin (FCP), a marker of intestinal inflammation, could be used to confirm this inflammatory status and to test its diagnostic performance in differentiating NCWS from irritable bowel syndrome/functional dyspepsia (IBS/FD). We conducted a multicenter study, comparing NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge, with IBS/FD subjects. In the retrospective phase, FCP values were analyzed to define the prevalence of its positivity and its role as a NCWS diagnostic biomarker. In the prospective phase we tested the effects of a strict 6-month wheat-free diet (WFD) on FCP values. 31.3% (n = 63/201) of NCWS patients had above normal FCP values (NCWS FCP +), whereas all IBS/FD patients proved negative (P = 0.0001). FCP using a cut-off value > 41 µg/g showed a 58.6% sensitivity and a 98.0% specificity (AUC 0.755, 95% C.I. 0.702–0.837) in distinguishing NCWS from IBS/FD patients. Of the 63 NCWS FCP+, 65.1% had negative FCP values after ≥ 6 months of WFD, with a significant reduction in FCP values (P < 0.0001). All NCWS FCP- subjects still preserved negative FCP values after ≥ 6 months of WFD. Our study showed that FCP can be a useful but supplementary diagnostic marker for differentiating between NCWS and IBS/FD. Strict WFD adherence reduced FCP values, normalizing them in 65.1% of NCWS FCP + subjects. These data suggest the existence of two NCWS subgroups: NCWS FCP + characterized by a probable predominantly inflammatory/immunologic pattern and NCWS FCP− featuring non-immuno-mediated etiopathogenetic mechanisms. (Registration number NCT01762579).

A22 INVESTIGATING THE EFFECTS OF DIET TRIGGER DISCLOSURE ON BEHAVIOUR IN IRRITABLE BOWEL SYNDROME (IBS) PATIENTS WITH PERCEIVED GLUTEN SENSITIVITY

Abstract Background Patients with self-perceived gluten sensitivity often undergo double-blinded, placebo-controlled (DBPC) challenge studies to determine whether gluten or wheat trigger their symptoms. However, it is unknown whether the result disclosure impacts patients’ beliefs and dietary choices. Aims To evaluate the impact of disclosing results of DBPC challenge with gluten and wheat on beliefs and dietary choices in IBS patients who adopt a gluten-free diet (GFD). Methods We conducted a DBPC crossover trial in 28 adult IBS patients (Rome IV) who previously reported improvement of symptoms while on a GFD. Patients were on a GFD throughout the study and were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low-FODMAP cereal bars, followed by 2-week washouts. Genetic predisposition to celiac disease and anti-gliadin IgG (AGA) were assessed. At least 6 months after the study completion, patients were contacted to assess their current diet, dietary beliefs, and symptoms prior to disclosing their study results. We assessed the same outcomes one month later. Statistical comparisons used paired Wilcoxon signed rank tests. Results The DBPC study showed similar proportions of participants reacting to wheat, gluten, and nocebo challenge, with greater symptoms after wheat compared to baseline (P&amp;lt;0.05). AGA IgG were present in 8% (2/25) and celiac disease-related genes in 80% (20/25) of patients. Out of 28 participants, 26 completed the pre-disclosure and 25 completed post-disclosure follow-up. All participants (N=26) believed that at least one challenge triggered their symptoms: whole wheat N=22, pure gluten N=23, nocebo N=2. Prior to disclosure, 17 participants continued while 9 abandoned the GFD; none changed their diet post-disclosure. Reasons to stay on the GFD included belief in its efficacy (N=16) and better quality of life (N=15), while reasons for abandoning included difficulty to adhere to the GFD and its cost (N=6) and losing belief in its efficacy (N=3). IBS symptoms did not change pre- vs. post-disclosure. Participants not reacting to wheat or gluten challenge expressed slightly lower median belief in GFD efficacy pre- vs. post-disclosure (80%, IQR [64%, 97%] vs 71%, IQR [48%, 78%]; P=0.03; Figure 1). Those worsening after wheat or gluten did not change their beliefs. Conclusions Although most IBS patients with self-perceived gluten sensitivity had celiac disease predisposition, only some reacted to gluten or wheat. Furthermore, after disclosing the study results, all participants maintained their dietary habits avoiding gluten, thus suggestive of strong central mechanisms underlying their symptoms. Figure 1. Belief in GFD efficacy pre- vs. post-disclosure of study results. Funding Agencies CIHRSociety for the Study of Celiac Disease, Nestle

Low-Dose Oral Wheat Challenge Contributes to Early Tolerance Acquisition in Children with Wheat Allergy: A Propensity Score Matched Retrospective Cohort Study

Low-Dose Oral Wheat Challenge Contributes to Early Tolerance Acquisition in Children with Wheat Allergy: A Propensity Score Matched Retrospective Cohort Study

Anemia in non-celiac wheat sensitivity: Prevalence and associated clinical and laboratory features.

Patients suffering from non-celiac wheat sensitivity (NCWS) frequently report extra-intestinal symptoms, such as anemia. We investigated the prevalence and associated clinical features of anemia in NCWS patients. Data from 244 NCWS patients, diagnosed by double-blind placebo-controlled wheat challenge, were retrospectively reviewed and compared with 2 control groups (celiac disease (CD) and irritable bowel syndrome (IBS)). Furthermore, 31 NCWS anemic patients were prospectively re-evaluated after at least 12 months on the "strict" wheat-free diet (WFD). Anemia prevalence in NCWS patients was 34.8% (mean hemoglobin 10.4±1.4g/dl), significantly higher than in IBS (17.4%, P=0.03), but not in CD ones. The NCWS group, on the whole, had sideropenic-like features with low serum iron and altered iron deposits. Both anemia prevalence and sideropenic-like features were more evident in CD than in NCWS patients, whereas only a few IBS subjects showed such features. Significant differences were found in anemic vs non-anemic NCWS patients as regards to female sex, diagnostic delay, poly/hypermenorrhea, iron deficiency, and higher TSH values. A long-term WFD significantly reduced anemia and improved iron metabolism. Microcytic/hypochromic anemia and altered iron metabolism occur frequently in NCWS and can be treated with a long-term strict WFD. NCWS should be included in differential diagnosis of anemic patients with "functional gastrointestinal troubles".

A19 INVESTIGATING MECHANISMS THAT DRIVE SYMPTOMS IN IRRITABLE BOWEL SYNDROME PATIENTS WITH PERCEIVED GLUTEN SENSITIVITY

Abstract Background Patients with irritable bowel syndrome (IBS) often report gastrointestinal symptoms after consuming wheat and gluten-containing foods. It is, however, unclear whether gluten is the main driver of symptoms, as other immunogenic peptides, such as amylase trypsin inhibitors (ATI), poorly digestible fiber (inulin, part of FODMAP) or even the nocebo effect may contribute to symptom generation. Purpose To evaluate whether whole wheat containing ATIs and/or purified gluten trigger gastrointestinal symptoms compared to nocebo in patients with IBS adopting a gluten-free diet (GFD). Method We conducted a double-blind, randomized, nocebo-controlled crossover study in adult IBS patients (Rome IV criteria) who previously perceived improvement of symptoms while on a GFD. The study was approved by the Hamilton Research Ethics Board (HiREB #4367). Participants were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low FODMAP cereal bars. Each challenge was followed by a 2-week washout. Patients remained on a GFD throughout the study, diet adherence was assessed by a dietitian and stool gluten immunogenic peptides (GIP; Biomedal). Gastrointestinal symptoms were assessed by IBS Symptom Severity Score (IBS-SSS); increases &amp;gt;50 points were considered a significant worsening. Blood samples were collected to assess immune markers and celiac (HLA DQ2, DQ8 and DQ7) genotype. Statistical comparisons used Friedman rank sum tests and paired Wilcoxon signed rank tests. Result(s) Twenty-nine IBS patients (27 female, mean age=42, SD=14.4 years) were enrolled in the study; 1 dropped. Similar proportions of patients reacted symptomatically to wheat (11/28, 39.3%), gluten (10/28, 35.7%) and nocebo (8/28, 28.6%). However, there was an overall significant increase in IBS symptoms after wheat (+39.5 on IBS-SSS; p=0.030) but not after gluten (+27.5; p=0.051) or nocebo (+5.5; p=0.236) challenges (Figure 1). Ten participants experienced IBS-SSS symptoms &amp;gt;175 during baseline and did not worsen further during the challenges. TNF-α trended from 1.35 pg/mL after nocebo, 1.47 pg/mL after gluten, to 1.57 pg/mL after wheat; however, this was not significant. Baseline adherence to a GFD was rated excellent in 19 (68%), good in 6 (21%), and fair in 3 (11%) participants. Median GIP levels were 0.584 µg/g after wheat, 0.432 µg/g after gluten, and 0.095 µg/g after nocebo; p&amp;lt;0.0001. Celiac predisposition genes were present in 19/24 participants (10/24 had DQ2, 2/24 had DQ8, and 9/24 had DQ7). Image Conclusion(s) IBS patients self-reporting wheat or gluten sensitivity had worse symptoms after whole wheat, but not purified gluten or nocebo challenge. However, similar proportions of IBS patients reacted to each intervention, suggesting that central mechanisms play an important role in symptom genesis. Furthermore, one third of patients had high symptoms during a GFD and did not react to wheat or gluten challenges, suggesting that other mechanisms are driving their IBS symptoms. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Society for the Study of Celiac Disease (Nestle); Canadian Digestive Health Foundation Disclosure of Interest None Declared

Global Wheat Head Detection Challenges: Winning Models and Application for Head Counting.

Data competitions have become a popular approach to crowdsource new data analysis methods for general and specialized data science problems. Data competitions have a rich history in plant phenotyping, and new outdoor field datasets have the potential to embrace solutions across research and commercial applications. We developed the Global Wheat Challenge as a generalization competition in 2020 and 2021 to find more robust solutions for wheat head detection using field images from different regions. We analyze the winning challenge solutions in terms of their robustness when applied to new datasets. We found that the design of the competition had an influence on the selection of winning solutions and provide recommendations for future competitions to encourage the selection of more robust solutions.

AN ADOLESCENT CASE OF HAE-NL-C1INH (WHO WAS) MISDIAGNOSED WITH WHEAT ALLERGY AND MULTIPLE DRUG ALLERGIES

Hereditary angioedema (HAE) is frequently misdiagnosed as drug allergy. It is essential to differentiate HAE from allergy. Diagnosing HAE-normal-C1INH (conventional HAE type III), presenting normal C1-INH, is even more difficult. Here, we report a case of a 17-year-old female diagnosed with HAE and having labeled wheat and multiple drug allergies. She had been suffering from skin edema and abdominal symptoms since childhood. After taking wheat at 13 years old, she had multiple episodes of the same symptoms. Wheat allergy was suspected, and she started eliminating wheat. Multiple attacks were observed after several drug use, and drug allergy was labeled. However, her attacks did not improve after eliminating wheat and the suspected drugs. Her C4 and C1-INH activity was normal, but we diagnosed her with HAE-normal-C1INH based on her family history, multiple attacks after dental procedures, ineffective antihistamines, and significant efficacy of C1-INH infusion. A double-blind, placebo-controlled wheat challenge test at our hospital was negative, and wheat removal was lifted. Drugs could be de-labeled by allergic tests and history. Repeated attacks of unexplained edema and abdominal pain should be differentiated from HAE and lead to an appropriate diagnosis.

No Difference in Tolerance between Wheat and Spelt Bread in Patients with Suspected Non-Celiac Wheat Sensitivity.

Individuals with suspected non-celiac wheat sensitivity (NCWS) often report better tolerance of spelt (Triticum aestivum ssp. spelta) compared to wheat (Triticum aestivum ssp. aestivum) bakery products. This experience has neither been validated nor explained on a molecular level. Therefore, we performed blinded wheat and spelt bread challenge in this patient group. Twenty-four adults with a history of NCWS but suspected spelt tolerance were challenged in a single-blinded crossover design over six weeks with six different study breads each at 300 g per day for 4 days followed by a washout phase of 3 days. Study breads comprised spelt and wheat breads made either after a traditional (T) or a current (C) recipe, resulting in four bread types plus a gluten-free bread with 1.5% added oligosaccharides (+FODMAP) and a gluten-free bread with 5% added wheat gluten (+Gluten). The main outcome parameter was the Irritable Bowel Syndrome—Severity Scoring System, which was higher than self-estimated by the participants after spelt bread consumption (p = 0.002 for T; p = 0.028 for C) and lower for wheat bread (p = 0.052 for T; p = 0.007 for C), resulting in no difference between wheat and spelt bread tolerance. The +FODMAP bread was better tolerated than both T breads (p = 0.003 for spelt; p = 0.068 for wheat) and equally well tolerated as both C breads and +Gluten breads after normalization to the washout scores. Neither signs of inflammation nor markers for intestinal barrier integrity were influenced. Our data do not confirm, on an objective basis, the differences in expected symptoms resulting from wheat and spelt products, suggesting a strong nocebo effect for wheat and a placebo effect for spelt.

Loop-Mediated Isothermal Amplification for Detection of Plant Pathogens in Wheat (Triticum aestivum).

Wheat plants can be infected by a variety of pathogen species, with some of them causing similar symptoms. For example, Zymoseptoria tritici and Parastagonospora nodorum often occur together and form the Septoria leaf blotch complex. Accurate detection of wheat pathogens is essential in applying the most appropriate disease management strategy. Loop-mediated isothermal amplification (LAMP) is a recent molecular technique that was rapidly adopted for detection of plant pathogens and can be implemented easily for detection in field conditions. The specificity, sensitivity, and facility to conduct the reaction at a constant temperature are the main advantages of LAMP over immunological and alternative nucleic acid-based methods. In plant pathogen detection studies, LAMP was able to differentiate related fungal species and non-target strains of virulent species with lower detection limits than those obtained with PCR. In this review, we explain the amplification process and elements of the LAMP reaction, and the variety of techniques for visualization of the amplified products, along with their advantages and disadvantages compared with alternative isothermal approaches. Then, a compilation of analyses that show the application of LAMP for detection of fungal pathogens and viruses in wheat is presented. We also describe the modifications included in real-time and multiplex LAMP that reduce common errors from post-amplification detection in traditional LAMP assays and allow discrimination of targets in multi-sample analyses. Finally, we discuss the utility of LAMP for detection of pathogens in wheat, its limitations, and current challenges of this technique. We provide prospects for application of real-time LAMP and multiplex LAMP in the field, using portable devices that measure fluorescence and turbidity, or facilitate colorimetric detection. New technologies for detection of plant pathogen are discussed that can be integrated with LAMP to obtain elevated analytical sensitivity of detection.

Review of Wheat Value Chain in Ethiopia

In Ethiopia, agriculture contributes over 35.8 percent to the national gross domestic product (GDP), almost 90 percent of export and 72.7percent of employment. Wheat production in 2020 for Ethiopia was 5,100 thousand tons. Ethiopia is the second largest wheat producers in Sub Saharan Africa next to South Africa, with a potential expansion to 1.3 million hectare. The objective of this review is to identify wheat value chain the key actors and their roles in wheat value chain and challenges and opportunities of wheat value chain in Ethiopia. The main actors in the chain include producers, processor, assembler, wholesaler, retailers, and consumers whereas the indirect actors are financial institutions, governments, NGOs). Marketing channel is a business structure of interdependent organizations involved in the process of making the product or service available for consumption starting from product origin. In terms of regional production potential Oromia contributes (57%), Amhara (28%), SNNP (8.7%) and Tigray (6.2%). These show that there is a weak linkage among the wheat value chain actors in Ethiopia. One of the indicators for this weak linkage is the absence (very low level) of linkage between producers and millers few of the wheat produced is directly sold to millers. Keywords: Value Chain, Wheat, Ethiopia DOI: 10.7176/JAAS/77-03 Publication date: January 31 st 2022

Dynamic Color Transform Networks for Wheat Head Detection.

Wheat head detection can measure wheat traits such as head density and head characteristics. Standard wheat breeding largely relies on manual observation to detect wheat heads, yielding a tedious and inefficient procedure. The emergence of affordable camera platforms provides opportunities for deploying computer vision (CV) algorithms in wheat head detection, enabling automated measurements of wheat traits. Accurate wheat head detection, however, is challenging due to the variability of observation circumstances and the uncertainty of wheat head appearances. In this work, we propose a simple but effective idea—dynamic color transform (DCT)—for accurate wheat head detection. This idea is based on an observation that modifying the color channel of an input image can significantly alleviate false negatives and therefore improve detection results. DCT follows a linear color transform and can be easily implemented as a dynamic network. A key property of DCT is that the transform parameters are data-dependent such that illumination variations can be corrected adaptively. The DCT network can be incorporated into any existing object detectors. Experimental results on the Global Wheat Detection Dataset (GWHD) 2021 show that DCT can achieve notable improvements with negligible overhead parameters. In addition, DCT plays an important role in our solution participating in the Global Wheat Challenge (GWC) 2021, where our solution ranks the first on the initial public leaderboard, with an Average Domain Accuracy (ADA) of 0.821, and obtains the runner-up reward on the final private testing set, with an ADA of 0.695.

Clinical Features of Wheat Allergy Are Significantly Different between Tri a 14 Sensitized Patients and Tri a 19 Sensitized Ones

Introduction: Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. Methods: With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. Results: Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (p < 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (p = 0.0017), a higher risk to be wheat allergic (p < 0.0001), a higher severity of the reactions (p < 0.00001) and a higher association with some cofactors, namely alcohol (p < 0.0005) and physical exercise (p = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (p < 0.0001), with a higher probability of patients being asymptomatic (p < 0.0001) and being sensitized to other foods, in particular to nuts and cereals (p < 0.00001). Conclusions: Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it’s more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance.

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity.

Background: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. Methods: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. Results: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. Conclusions: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this ‘atypical’ manifestation.

Clinical Characteristics and Proposed Wheat-Cofactor Challenge Protocol with a High Diagnostic Yield in Adult-Onset IgE-Mediated Wheat Allergy.

BackgroundIgE-mediated wheat allergy in adults can be childhood or adulthood onset. Adult-onset wheat allergy has been reported, but data on clinical characteristics and practical food challenge protocols are scarce.ObjectiveWe aimed to describe the clinical characteristics of adult-onset wheat allergy, laboratory results, and outcomes of a modified 3-day challenge protocol using a combination of aspirin, wheat, and exercise.Patients and MethodsPatients with histories compatible with adult-onset wheat allergy were recruited from Siriraj Hospital, Thailand. Clinical history, skin prick tests (SPTs), and specific IgE (sIgE) levels were ascertained. Patients with no food challenge contraindications were asked to volunteer for wheat challenge. A modified 3-day protocol using 300 mg of acetylsalicylic acid, 60–75 g of wheat flour, and exercise was used for confirmatory diagnosis of conventional wheat allergy (WA) and wheat-dependent exercise-induced anaphylaxis (WDEIA).ResultsThirty-three patients were recruited. The mean age of onset was 29.7 years (SD 10.5). SPTs yielded positivity rates of 9.1%, 84.8%, and 81.8% in commercial wheat, in-house gliadin, and in-house glutenin extracts, respectively. sIgE yielded a positivity rate of 61% and 88% in wheat and ω5-gliadin, respectively. Eighteen patients underwent oral wheat challenges. Of these, 17 patients (94.4%) had positive challenges leading to definite diagnoses of WA (35%), and WDEIA (65%). One WDEIA patient developed hypotensive anaphylaxis in the protocol.ConclusionWDEIA was the most common phenotype. Our modified 3-day protocol could differentiate WA and WDEIA and yielded a high positivity rate (94.4%). It should be used cautiously as severe reactions can occur.

Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial.

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.

Non-celiac wheat sensitivity: a search for the pathogenesis of a self-reported condition

A significant percentage of the general population reports gastrointestinal and non-gastrointestinal symptoms caused by wheat and/or gluten ingestion, even though they do not suffer from celiac disease (CD) or wheat allergy (WS), because they test negative both for CD-specific serology and histopathology. All patients report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). The objective of this paper was to review some studies regarding the pathogenesis of NCGS to summarize the current hypotheses about the mechanisms, which can lead to NCGS. Particular attention was given to the immunologic and the malabsorptive hypotheses. We reviewed data of our previous studies involving patients diagnosed with NCWS by means of double-blind placebo-controlled wheat challenge. The data indicating a possible wheat allergy diagnosis were examined and other data in the literature were reviewed; we also reviewed the putative role of fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAPs) and of α-amylasetrypsin inhibitors (ATIs) proteins in the NCGS pathogenesis. NCGS pathogenesis has been attributed to very different mechanisms, among others: i) activation of innate and adaptive immunity (the immune/allergic mechanisms) induced by gluten or the non-gluten ATI family; ii) incomplete digestion and/or absorption of FODMAPs (the intolerance mechanisms); and iii) psychological effect.We suggest that NCGS is a heterogeneous condition, which includes different subgroups of patients who have different pathogenic mechanisms: strong data suggest a direct pathogenic immunogenic/inflammatory role of wheat-cereal proteins (not only gluten) in a subgroup, probably the largest, of these patients.

Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity

Studies of non-celiac gluten or wheat sensitivity (NCGWS) have increased but there are no biomarkers of this disorder. We aimed to evaluate histologic features of colon and rectal tissues from patients with NCGWS. We performed a prospective study of 78 patients (66 female; mean age, 36.4 years) diagnosed with NCGWS by double-blind wheat challenge at 2 tertiary care centers in Italy, from January 2015 through September 2016. Data were also collected from 55 patients wither either celiac disease or self-reported NCGWS but negative results from the wheat-challenge test (non-NCGWS controls). Duodenal and rectal biopsies were collected and analyzed by immunohistochemistry to quantify intra-epithelial CD3+ T cells, lamina propria CD45+ cells, CD4+ and CD8+ T cells, mast cells, and eosinophils and to determine the presence and size of lymphoid nodules in patients with NCGWS vs patients with celiac disease or non-NCGWS controls. Duodenal tissues from patients with NCGWS had significantly higher numbers of intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than duodenal tissues from non-NCGWS controls. Duodenal tissues from patients with NCGWS and dyspepsia had a higher number of lamina propria eosinophils than patients with NCGWS without upper digestive tract symptoms. Rectal mucosa from patients with NCGWS had a larger number of enlarged lymphoid follicles, intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than rectal mucosa from non-NCGWS controls. Duodenal and rectal mucosal tissues from patients with celiac disease had more immunocytes (CD45+ cells, CD3+ cells, and eosinophils) than tissues from patients with NCGWS or non-NCGWS controls. We identified markers of inflammation, including increased numbers of eosinophils, in duodenal and rectal mucosa from patients with NCGWS. NCGWS might therefore involve inflammation of the entire intestinal tract. Eosinophils could serve as a biomarker for NCGWS and be involved in its pathogenesis. Clinicaltrials.gov: NCT01762579.

Non-celiac gluten or wheat sensitivity: It's complicated!

In the last 30years, non-celiac gluten sensitivity (NCGS) has emerged as an intriguing and controversial topic in gastroenterology. The diagnosis of NCGS/NCWS requires a symptomatic reaction to gluten, or wheat-containing food, and remission of symptoms with gluten or wheat challenge, in patients in whom celiac disease and wheat allergy have been excluded. There have been several randomized clinical trials (RCT) addressing this issue which have produced controversial results. In this issue of Neurogastroenterology and Motility, a double-blind placebo-controlled randomized trial in patients with suspected NCGS on GFD, did not reproduce symptoms after gluten intake compared to placebo. This mini-review addresses outstanding issues related to the diagnosis of NCGS/NCWS as well as areas of interest for future studies that could explain, in part, the controversy in this area.

Evaluation of the results of oral food challenges conducted in specialized and general hospitals.

BackgroundOral food challenge (OFC) tests are conducted in both specialized institutions and general hospitals. We aimed to compare the severity of the conditions of the patients between these 2 types of institutions in order to consider the role of such institutions in society.ObjectiveWe evaluated the results of OFC tests for hen's egg, cow's milk, and wheat that were conducted in a specialized institution (Aichi Children's Health and Medical Center [ACHMC], n = 835) and in 4 general hospitals (n = 327) in Aichi prefecture, Japan.MethodsThe symptoms provoked were scored using the total score (TS) of the Anaphylaxis Scoring Aichi scoring system in combination with the total ingested protein dose (Pro) before the appearance of allergic symptoms.ResultsThe total ingested dose of the challenge-positive patients in ACHMC was significantly less than that in the general hospitals (p < 0.01). The median TS of the provoked symptoms in ACHMC and the general hospitals did not differ to a statistically significant extent in the hen's egg or cow's milk challenges; however, the median TS in ACHMC was significantly lower than that in the general hospitals for the wheat challenge (p = 0.02). The median TS/Pro values in ACHMC were almost identical to the upper 25% of the TS/Pro values in the general hospitals, suggesting that the specialized institution usually managed more severe patients.ConclusionThe specialized institution performed OFC tests at a lower threshold dose, but provoked similar TSs to the general hospitals. This evaluation may help in optimizing the distribution of patients to general hospitals and specialized institutions.

Safety evaluation of a β-amylase food enzyme obtained from wheat (Triticum spp.).

The food enzyme considered in this opinion is a β‐amylase (EC 3.2.1.2), obtained from the grain of wheat (Triticum spp.) by Roquette (France). The β‐amylase is intended to be used in starch processing for production of glucose syrups containing maltose to be used as a food ingredient. Since the presence of residual amounts of total organic solids (TOS) in glucose syrups after filtration and purification during starch processing is negligible, no dietary exposure was calculated. As the food enzyme is derived from edible parts of wheat, no toxicological tests are required. Wheat is known as a gluten‐containing cereal. However, the gluten content of the food enzyme was shown to be below the limit of quantification of the applied analytical method and well below the threshold value of 20 mg/kg for ‘gluten‐free’ products. Furthermore, the potential allergenicity was evaluated by searching for similarity between the amino acid sequence of the β‐amylase and the sequences of known food allergens; no match was found. Although β‐amylase from wheat is described as a potential occupational respiratory allergen, and oral wheat challenges in wheat allergic patients may result in clinical symptoms, the enzyme and the low levels of other wheat proteins will be removed from the final food ingredients through a downstream purification process. Based on the origin of the food enzyme from edible parts of grain, the manufacturing process, and the compositional and biochemical data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.