Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice.

People with celiac disease or gluten sensitivity may experience an immune reaction to the protein called gluten, which is present in wheat, barley, and rye. A strict gluten-free diet is the sole cure for these ailments. There are chances of food fraud about the claim of being gluten-free food items. As a result, there is a rising need for trustworthy and precise ways to identify gluten. There are many methods to detect gluten in food samples viz., enzyme-linked immunosorbent assay 1 Surface plasmon resonance (SPR), Electrochemical sensors, Fluorescence-based sensors, etc. The use of sensors is one of the most promising methods for gluten detection. For detecting gluten, a variety of sensors, including optical, electrochemical, and biosensors, have been developed with different limits of detection and sensitivity. The present review reports the recent advancements (2019-2023) in the development of sensors for gluten detection in food. We may conclude that sensitivity and limit of detection are not related to the type of sensor used (aptamer or antibody-based), however, there are advancements, with the year, on the simplicity of the material used like paper-based sensors and paradigm shift to reagent free sensors by the spectral analysis. Also, recent work shows the potential of IoT-based studies for gluten detection.

UNASSIGNED: Gluten allergy is a major public health problem that is growing at an alarming rate. Specific mechanisms underlying sensitization to gluten remain incompletely understood. Currently, it is unclear whether chronic exposure to alcohol-soluble gluten extract via undamaged skin has the capacity to clinically sensitize mice for life-threatening anaphylaxis. Using an adjuvant-free mouse model, here we tested the hypothesis that chronic application of alcohol-soluble durum gluten (ASDG) extract will clinically sensitize mice for life-threatening anaphylaxis.
UNASSIGNED: This study was conducted in a gluten-free Balb/c mouse colony that was established and maintained on a plant protein-free diet. Groups of adult female mice were exposed dermally to ASDG extract or vehicle once a week for 9-weeks. Specific (s) and total (t) IgE levels were quantified. Mice were challenged systemically with ASDG to measure symptoms of systemic anaphylaxis. Hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR) were determined upon challenge. Spleen Th1, Th2, and other immune markers were quantified.
UNASSIGNED: We found that chronic exposure to ASDG elicited robust elevation of sIgE and tIgE. Systemic challenge with ASDG, but not vehicle, elicited life-threatening anaphylaxis associated with dramatic HSR and MMCR. Correlation analysis demonstrated direct positive inter-relationships among IgE, HSR, and MMCR. Anaphylaxis was associated with significant elevation of prototypic Th2 but not Th1 immune markers in the spleen.
UNASSIGNED: Our study collectively demonstrates that ASDG is intrinsically allergenic; and chronic exposure to ASDG via undamaged skin can clinically sensitize mice for life-threatening anaphylaxis via activating the systemic Th2 immune responses.

BACKGROUND: A large number of people worldwide suffer from gluten-induced food allergy. As investigated in our previous research, Lactobacillus paracasei AH2 isolated from traditionally homemade sourdough in Anhui province of China showed the potential to reduce the immune reactivity of wheat protein by in vitro evaluation. However, whether L. paracasei AH2 has a role in alleviating wheat allergy in an in vivo model and its underlying mechanisms have not been elucidated.
RESULTS: In this study, the alleviative effects of L. paracasei AH2 on gluten-induced allergic response were evaluated. Compared with a gluten-allergic mouse, L. paracasei AH2 suppressed anaphylaxis symptoms, gluten-specific immunoglobulin E, histamine and interleukin-4. Moreover, L. paracasei AH2 attenuated splenomegaly and induced Th1 or Treg cell differentiation to modulate the Th1/Th2 immune balance toward Th1 polarization. Short-chain fatty acid (SCFA) levels were enhanced after L. paracasei AH2 supplementation, contributing to allergy relief as well as reducing the pH of colonic contents. The α and β diversities of the gut microbiota were modulated by L. paracasei AH2 with increased relative abundance of Lacticaseibacillus and SCFA producers (Faecalibaculum, Alloprevotella and Bacteroides genera), as well as decreased unfavorable Lachnospiraceae_NK4A136_group and Alistipes. Additionally, L. paracasei AH2 protected the intestinal barrier function by upregulating tight junctions and improved the antioxidant activities in serum.
CONCLUSIONS: Our findings indicate that L. paracasei AH2 could act as a potential probiotic for relieving wheat allergy by modulating the gut microbiota and elevating SCFA levels. © 2023 Society of Chemical Industry.

Recent research consensus has highlighted the role of intestinal luminal factors in the association between intestinal microenvironment homeostasis and food allergy. However, the association between intestinal immune homeostasis and food allergy-related proteomic features remains elusive. In this study, we aimed to investigate the changes in gluten allergy (GA)-defined phenotypes and endotypes and intestinal microenvironment factors in BALB/c mice and linked GA to colonic proteomic signatures. Combined with increased allergy and diarrhea scores, intense antibody responses and abnormalities in T-cell cytokine production were induced in mice. GA-associated disruption of intestinal microenvironment homeostasis was underlined by the increased colonic pH, decreased intestinal antioxidant capacity, impaired intestinal barrier function, and decreased production and imbalanced proportions of short-chain fatty acids. 16S rRNA amplicon sequencing showed that the gut microbiota dysbiosis in mice was characterized by significant enrichment of six bacterial taxonomic units, including Prevotellaceae, Escherichia Shigella, Alloprevotella, Escherichia coli, Bacteroides vulgatus, and Lachnospiraceae bacterium DW59, which was correlated with immune end points. Using a label-free proteomics quantitative approach, 24 differentially expressed proteins linking GA-induced gut dysbiosis were identified, with four of them enriched in the serine endopeptidase inhibitor activity pathway. The development of GA in mice was associated with changes in specific intestinal luminal factors and may be mediated by serine protease activity-associated metabolic routes.

Adequate folate intake during the female reproductive years plays a vital role in fetal neurodevelopment. To address this public health concern, the FDA required enriched cereal grains to be fortified with folic acid. A positive outcome of fortification with folic acid was a reduction in the number of pregnancies affected by neural tube defects (NTDs). However, there are individuals unable to consume these enriched grains, such as those with a gluten allergy or intolerance. The need for folic acid fortification across all grains, those with and without gluten, should be considered in an effort to provide equivalent folic acid to all and further promote public health efforts aimed at decreasing the incidence of NTDs.

OBJECTIVE: CD4(+) T cells specific for dietary gluten and interleukin 15 (IL15) contribute to the pathogenesis of celiac disease. We investigated whether and how they interact to damage the intestine using mice that overexpress human IL15 in the intestinal epithelium and have CD4(+) T cells specific for ovalbumin, a dietary antigen.
METHODS: We crossed mice with CD4(+) T cells specific for ovalbumin (OTII) with mice that overexpress human IL15 under an intestine-specific promoter (B6 × IL15Tge). The offspring (OTII × IL15Tge mice) received control or ovalbumin-containing diets until 3 months of age. Enteropathy was monitored by weight, ratio of villous:crypt length, and the number of intestinal lymphocytes. Phenotype, cytokine production, and degranulation of mucosal and spleen lymphocytes were analyzed by multicolor flow cytometry or enzyme-linked immunosorbent assay. Regulatory T-cell function and CD8(+) T-cell activation were analyzed in co-culture assays.
RESULTS: Exposure to ovalbumin reduced growth and led to enteropathy in OTII × IL15Tge mice but not in control OTII × B6 littermates. Enteropathy was associated with expansion of mucosal granzyme B(+) CD8(+) T cells, and developed despite increased frequency of functional ovalbumin-specific regulatory T cells. Ovalbumin-activated CD4(+) T cells secreted IL2, which along with IL15 stimulated expansion of noncognate intestinal cytotoxic CD8(+) T cells, which did not respond to regulatory T cells and induced epithelial damage.
CONCLUSIONS: We observed that in mice given food antigen, cooperation between IL15 and CD4(+) T cells is necessary and sufficient to activate CD8(+) T cells and damage the small intestine. We propose that this process is involved in the development of celiac disease.

OBJECTIVE: Celiac disease shares features of other disorders. It can be diagnosed conclusively only based on duodenal histology analysis, which is not practical for screening purposes. Serologic analysis might be used to identify candidates for biopsy analysis. We aimed to develop a simple diagnostic approach that all clinicians could follow to increase the percentage of patients accurately diagnosed with celiac disease at initial presentation.
METHODS: We performed a retrospective analysis of data from 752 patients (88 with celiac disease, none were IgA deficient) who attended a UK district general hospital from January 2007 through December 2008 and underwent biopsy analysis and serologic tests to measure endomyseal antibodies and IgA antibodies against tissue transglutaminase (tTG). Patients avoiding gluten in their diet were excluded. Patients were assigned to 1 of 4 groups: high-risk (based on presence of anemia, chronic diarrhea, unintentional weight loss, or dermatitis herpetiformis), low-risk (based on such factors as dyspepsia, abnormal liver function, ataxia, or chronic cough), nutrient deficiency (based on levels of iron, vitamins B12 and D, or folate), or screening (because they had type 1 diabetes or a family history of celiac disease). Patients with celiac disease were identified using the modified Marsh criteria (grades 1-3) for interpreting duodenal histology. We compared clinical category, serology profiles, and biopsy results between patients with and without celiac disease.
RESULTS: Celiac disease was diagnosed in 64 of 565 patients in the high-risk group (11%), 14 of 156 patients in the low-risk group (9%; P = .47 compared with high-risk group), 7 of 28 patients in the nutrient-deficiency group, and 3 of 3 patients in the screening group. Among 71 patients who tested positive for both antibodies (tTG and endomyseal antibodies), the positive predictive value for celiac disease was 97%; a negative test result for tTG had a negative predictive value of 98%. Among 708 patients with normal-looking biopsy samples, only 62 had celiac disease (9%). Among 44 patients with abnormal biopsy samples, 26 had celiac disease (59%).
CONCLUSIONS: Based on a retrospective analysis, patients with and without celiac disease cannot be distinguished based on clinical features. Patients who present with symptoms of celiac disease should be tested for tTG, to identify candidates for duodenal biopsy analysis.

OBJECTIVE: Transaminasemia develops via different pathways in patients with celiac disease; no information is available on risk factors specifically attributable to celiac disease.
METHODS: We analyzed data collected from consecutive patients referred from January 1997 through December 2009 to the celiac disease clinic at the Spedali Civili of Brescia, Italy. We assessed the factors affecting hypertransaminasemia in 683 patients with celiac disease (based on serologic and biopsy analysis, cohort A; 34 ± 14 years of age) and 304 with functional syndromes (cohort B; 37 ± 13 years of age).
RESULTS: Hypertransaminasemia was detected in 138 patients in cohort A (20%). It was associated with malabsorption (odds ratio [OR], 2.22; P = .004), diarrhea (OR, 1.72; P = .005), and increasing severity of mucosal lesion (Marsh-Oberhuber class; OR, 1.46; P = .001) but not with body mass index (BMI) or the serum level of tissue-transglutaminase antibodies (tTG). Hypertransaminasemia was detected in 22 patients in cohort B (7%) and was associated with the World Health Organization\'s BMI categories (OR, 7.9; P < .001). In subsets of patients studied with the same analytical method (313 of cohort A and 188 of cohort B), the level of tTG was significantly higher in cohort A at baseline (25.2 ± 16.9 U/L aspartate aminotransferase [AST]) than in cohort B (20.6 ± 9.9 U/L AST, P < .0001) and was related to BMI in cohort B (P = .0012) but not cohort A. When patients were placed on gluten-free diets, the levels of AST decreased from 25.2 ± 16.9 U/L to 19.9 ± 6.6 U/L (P < .0001), independently of the changes of duodenal histology and tTG and correlated with BMI (P = .0007); the prevalence of hypertransaminasemia decreased from 13% to 4%.
CONCLUSIONS: Patients with celiac disease have a higher prevalence of hypertransaminasemia than controls (patients with functional syndromes). Hypertransaminasemia is related to the severity of the duodenal lesion and malabsorption but not BMI. By contrast, there was a positive correlation between the levels of AST and BMI in controls; this relationship was restored when patients with celiac disease were placed on gluten-free diets.