-
1.
Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.
Cartee, AK, Choung, RS, King, KS, Wang, S, Dzuris, JL, Anderson, RP, Van Dyke, CT, Hinson, CA, Marietta, E, Katzka, DA, et al
The American journal of gastroenterology. 2022;(2):319-326
Abstract
INTRODUCTION Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.
-
2.
Effect of Gluten Ingestion and FODMAP Restriction on Intestinal Epithelial Integrity in Patients with Irritable Bowel Syndrome and Self-Reported Non-Coeliac Gluten Sensitivity.
Ajamian, M, Rosella, G, Newnham, ED, Biesiekierski, JR, Muir, JG, Gibson, PR
Molecular nutrition & food research. 2021;(5):e1901275
Abstract
SCOPE Since epithelial barrier dysfunction has been associated with gluten and fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAPs), the effect of alterations in FODMAP a gluten intake on epithelial barrier function in patients with irritable bowel syndrome (IBS) who self-reported gluten sensitivity. METHODS AND RESULTS Circulating concentrations of markers of epithelial injury (syndecan-1 and intestinal fatty acid-binding protein) and bacterial translocation (lipopolysaccharide-binding protein and soluble CD14) are measured while consuming habitual gluten-free diet and during blinded challenges with gluten or placebo on a background of low FODMAP intake. In 33 patients, only syndecan-1 concentrations during their habitual diet are elevated (median 43 ng mL-1 ) compared with 23 ng mL-1 in 49 healthy subjects (p < 0.001). On a low FODMAP diet, symptoms are reduced and levels of syndecan-1 (but not other markers) fell by a median 3335% (p < 0.001) irrespective of whether gluten is present or not. CONCLUSION Gluten ingestion has no specific effect on epithelial integrity or symptoms in this cohort, but reducing FODMAP intake concomitantly reduces symptoms and reverses apparent colonic epithelial injury. These findings highlight the heterogeneity of populations self-reporting gluten sensitivity and implicate FODMAPs in colonic injury in IBS.
-
3.
Oral Consumption of Bread from an RNAi Wheat Line with Strongly Silenced Gliadins Elicits No Immunogenic Response in a Pilot Study with Celiac Disease Patients.
Guzmán-López, MH, Sánchez-León, S, Marín-Sanz, M, Comino, I, Segura, V, Vaquero, L, Rivero-Lezcano, OM, Pastor, J, Sousa, C, Vivas, S, et al
Nutrients. 2021;(12)
Abstract
Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD.
-
4.
Gastrointestinal microbiome and gluten in celiac disease.
Wu, X, Qian, L, Liu, K, Wu, J, Shan, Z
Annals of medicine. 2021;(1):1797-1805
-
-
Free full text
-
Abstract
Coeliac disease (CD), also known as gluten sensitive enteropathy, is an autoimmune intestinal disease induced by gluten in genetically susceptible individuals. Gluten is a common ingredient in daily diet and is one of the main environmental factors to induce coeliac disease. Adhering to gluten free diet (GFD) is an effective method for treating CD. Microbiota plays an extremely important role in maintaining human health, and diet is the main factor to regulate the composition and function of gut microbiota. Recent studies have shown that gluten metabolism is closely related to gastrointestinal tract (GIT) microbiota. With the increasing prevalence of coeliac disease, there is a need for alternative treatments to GFD. In this review, biological medication of gluten, relationship between gluten and gut microflora, effect of GFD on GIT microflora, and effect of probiotics on CD were reviewed. By analysing the research progress on relationship between gluten and gastrointestinal microbiome in coeliac disease, this review tried to explore the prospective and potential mechanism of microecological agents in treating coeliac disease.
-
5.
A Sensitive Whole Blood Assay Detects Antigen-Stimulated Cytokine Release From CD4+ T Cells and Facilitates Immunomonitoring in a Phase 2 Clinical Trial of Nexvax2 in Coeliac Disease.
Hardy, MY, Goel, G, Russell, AK, Chen Yi Mei, SLG, Brown, GJE, Wang, S, Szymczak, E, Zhang, R, Goldstein, KE, Neff, KM, et al
Frontiers in immunology. 2021;:661622
Abstract
Improved blood tests assessing the functional status of rare gluten-specific CD4+ T cells are needed to effectively monitor experimental therapies for coeliac disease (CD). Our aim was to develop a simple, but highly sensitive cytokine release assay (CRA) for gluten-specific CD4+ T cells that did not require patients to undergo a prior gluten challenge, and would be practical in large, multi-centre clinical trials. We developed an enhanced CRA and used it in a phase 2 clinical trial ("RESET CeD") of Nexvax2, a peptide-based immunotherapy for CD. Two participants with treated CD were assessed in a pilot study prior to and six days after a 3-day gluten challenge. Dye-dilution proliferation in peripheral blood mononuclear cells (PBMC) was assessed, and IL-2, IFN-γ and IL-10 were measured by multiplex electrochemiluminescence immunoassay (ECL) after 24-hour gluten-peptide stimulation of whole blood or matched PBMC. Subsequently, gluten-specific CD4+ T cells in blood were assessed in a subgroup of the RESET CeD Study participants who received Nexvax2 (maintenance dose 900 μg, n = 12) or placebo (n = 9). The pilot study showed that gluten peptides induced IL-2, IFN-γ and IL-10 release from PBMCs attributable to CD4+ T cells, but the PBMC CRA was substantially less sensitive than whole blood CRA. Only modest gluten peptide-stimulated IL-2 release could be detected without prior gluten challenge using PBMC. In contrast, whole blood CRA enabled detection of IL-2 and IFN-γ before and after gluten challenge. IL-2 and IFN-γ release in whole blood required more than 6 hours incubation. Delay in whole blood incubation of more than three hours from collection substantially reduced antigen-stimulated IL-2 and IFN-γ secretion. Nexvax2, but not placebo treatment in the RESET CeD Study was associated with significant reductions in gluten peptide-stimulated whole blood IL-2 and IFN-γ release, and CD4+ T cell proliferation. We conclude that using fresh whole blood instead of PBMC substantially enhances cytokine secretion stimulated by gluten peptides, and enables assessment of rare gluten-specific CD4+ T cells without requiring CD patients to undertake a gluten challenge. Whole blood assessment coupled with ultra-sensitive cytokine detection shows promise in the monitoring of rare antigen-specific T cells in clinical studies.
-
6.
Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease.
Monachesi, C, Verma, AK, Catassi, GN, Galeazzi, T, Franceschini, E, Perticaroli, V, Lionetti, E, Catassi, C
Nutrients. 2021;(1)
Abstract
A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2-18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5-20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.
-
7.
Gluten contamination in food services and industry: A systematic review.
Falcomer, AL, Santos Araújo, L, Farage, P, Santos Monteiro, J, Yoshio Nakano, E, Puppin Zandonadi, R
Critical reviews in food science and nutrition. 2020;(3):479-493
Abstract
Gluten-related disorders (GRD) affects approximately 10% of the general population. The only treatment for GRD is still so far is the lifelong complete exclusion of gluten from the daily diet. The correct information about the presence/absence of gluten in food is very important to this group. The present study aimed to evaluate the prevalence of gluten contamination in gluten-free industrial and non-industrial products. In this systematic review, 24 cross-sectional studies were analyzed. The authors developed specific search strategies for Science Direct, Scopus, Web of Science, Google Scholar and ProQuest Dissertations & Theses Global. The authors evaluated the methodological quality of the included studies using criteria from Meta-analysis of Statistics Assessment and Review Instrument (MASTARI). We performed the statistical meta-analysis by metafor package of R program. 95.83% (n = 23) of the studies presented positive results for contamination (over 20 ppm). In industrial food products, studies showed a contamination prevalence of 13.2% (95% CI: 10.8%-15.7%). In non-industrial food products, studies showed a contamination prevalence of 41.5% (95% CI: 16.6%-66.4%). Despite the non-industrial products presented higher contamination prevalence than the industrial products, the difference was not significant (p = 0.072). The findings indicate cross-contamination in industrialized and non-industrialized products. As expected, industrial products labeled as gluten-free showed a lower percentage of gluten-contamination than non-industrialized. Despite that, any contaminated sample found in this group present greater relevance than non-labeled foods. It indicates that foods labeled as "gluten-free" should not be considered safe for patients with GRD since information on the label regarding the presence/absence of gluten is unreliable. Therefore, any gluten-contamination in products labeled as gluten-free is a serious problem to whom present GRD. Further studies are needed to estimate gluten cross-contamination in food service meals and industry better.
-
8.
Pilot study on non-celiac gluten sensitivity: effects of Bifidobacterium longum ES1 co-administered with a gluten-free diet.
Di Pierro, F, Bergomas, F, Marraccini, P, Ingenito, MR, Ferrari, L, Vigna, L
Minerva gastroenterologica e dietologica. 2020;(3):187-193
Abstract
BACKGROUND Bifidobacterium longum ES1 is a strain probiotic, colonizing the human gut and capable of a degradative action on gliadin. In an attempt to find new nutritional solutions aimed at improving the quality of life of patients with non-celiac gluten sensitivity (NCGS) we evaluated the effectiveness of this strain, in association with a gluten-free diet, comparing its efficacy versus diet therapy alone. METHODS The experimental design included a non-randomized, open-label, 1:1 intervention study in parallel groups. Enrolled patients with symptoms attributable to NCGS, and with negative diagnoses of both wheat allergy and celiac disease, were included in this three-month trial divided into four outpatient visits (baseline, T1, T2 and T3). Fifteen patients for each group completed the experimental protocol. RESULTS Our results showed that a combination of diet and probiotic determined a more significant reduction in the frequency and intensity of intestinal and extra-intestinal symptoms, and a clear improvement in stool consistency. CONCLUSIONS Although the study was carried out on a small number of patients, the results of our pilot trial suggest that a combined strategy of naturally gluten-free diet therapy with administration of the probiotic strain ES1 appears to offer a greater advantage than the dietary regime alone in improving the clinical symptomatic picture and in stabilizing the intestinal microbiota.
-
9.
Allergic reactions to hydrolysed wheat proteins: clinical aspects and molecular structures of the allergens involved.
Tranquet, O, Larré, C, Denery-Papini, S
Critical reviews in food science and nutrition. 2020;(1):147-156
Abstract
Wheat gluten can be chemically or enzymatically hydrolysed to produce functional ingredients useful in food and cosmetics. However severe allergies to hydrolysed wheat proteins (HWP) have been described in Europe and Japan since the early 2000's. Triggering proteins and IgE epitopes were described both for French and Japanese cohorts and appeared remarkably similar leading to define a new wheat allergic entity. Deamidation induced by functionalisation generate neo-allergens responsible for this particular allergy. This article aims to review the processes leading to deamidation and the clinical features of the patients suffering from this allergy. Then the molecular determinants involved in HWP-allergy were exhaustively described and hypothesis regarding the sensitizing mechanism of HWP-allergy are discussed. Finally, current regulation and tools aiming at managing this risk associated with HWP are presented.
-
10.
[Not Available].
Providoli, N
Revue medicale suisse. 2020;(679):235-236