Gluten Sensitivity Research Articles

Attention-deficit Hyperactivity Disorder and Gluten Sensitivity in Children

Attention-deficit Hyperactivity Disorder and Gluten Sensitivity in Children

Recent advances in palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris.The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients.Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP.In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP.Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.

Non-Celiac Gluten Sensitivity in Children: Controversial Role of Gluten and Diagnostic Enigma

Non-celiac gluten sensitivity (NCGS) is a debatable condition that affects less than 6% of children. The absence of specific diagnostic markers and standardized diagnostic procedures make the diagnosis of NCGS challenging, covering patients with different and varied symptoms. Generally, the parents of small and younger children introduce a gluten-free diet (GFD) based on their personal experiences and expectations. Additionally, a “fad component” exists, contributing to the recent rise in the popularity of GFD. Thus, celiac disease (CD) and wheat allergy (WA) must be excluded as these also appear in individuals experiencing symptoms similar to those of NCGS, improving and worsening with gluten withdrawal and consumption, respectively. The role of gluten inducing gastrointestinal symptoms in individuals with self-reported NCGS has been skeptically assessed based on evidence in recent years. However, currently, it is unknown whether a strict GFD is necessary for patients with NCGS. Thus, the placebo-controlled gluten challenge remains the gold standard for a challenging diagnosis like NCGS. The present review evaluates the published studies based largely on the adult population and describes the key elements in diagnosing NCGS and differential diagnosis with CD and WA.

Transamidation Down-Regulates Intestinal Immunity of Recombinant α-Gliadin in HLA-DQ8 Transgenic Mice.

Enzymatic transamidation of gliadins by microbial transglutaminase (mTG) inhibits interferon-γ (IFN-γ) secretion by intestinal T cell lines in patients with celiac disease (CD). To gain insight into the cellular mechanisms underlying the down-regulatory effects of transamidation, we tested a single recombinant α-gliadin (r-gliadin) harbouring two immunodominant peptides, p13 (aa. 120–139) and p23 (aa. 220–239), in HLA-DQ8 transgenic mice, a model of gluten sensitivity. Mice were intranasally immunised with r-gliadin or r-gliadin transamidated by mTG (K-r-gliadin) along with cholera toxin, and the response of mesenteric lymph node cells was analysed by cytokine multiplex assay. An in vitro challenge with r-gliadin was characterised by secretion of specific cytokines featuring both innate immunity and the Th1/Th2/Th17 pattern of the adaptive response. Notably, transamidation specifically down-regulated the Th1 response. Structural studies performed on K-r-gliadin confirmed that specific glutamine residues in p13 and p23, previously found to be deamidated by tissue transglutaminase, were also transamidated by mTG. In silico analysis, simulating p13 and p23 peptide binding to HLA-DQ8 showed that these glutamines, in the form of glutamate, could interact by means of salt bridges with peculiar amino acids of the alpha chain of HLA-DQ8, suggesting that their transamidation may influence the HLA-restricted recognition of these peptides. Thus, the structural findings provided a rationale to explain the down-regulation of the r-gliadin-specific Th1 response following transamidation.

Recognition and management of rapid-onset gluten ataxias: case series

BackgroundMost immune-mediated cerebellar ataxias, including those associated with gluten sensitivity (Gluten Ataxia), tend to present subacutely and usually progress gradually. Acute presentations with rapid progression outside the context of paraneoplastic cerebellar degeneration require prompt diagnosis and early access to disease-modifying immunotherapy in order to avert severe and permanent neurological disability.Case presentationsWe describe three cases of rapid-onset Gluten Ataxia, an immune-mediated cerebellar ataxia due to gluten sensitivity. We detail their presentation, clinical and neuroimaging findings, and our treatment strategy with immunotherapy.ConclusionsOur cases highlight the potential for immune-mediated cerebellar ataxias to present acutely, with rapid-onset symptoms and devastating neurological consequences. We caution against the diagnosis of ‘post-infective cerebellitis’ in adults, and advocate early consideration of an immune-mediated cerebellar ataxia and initiation of immunotherapy to prevent irreversible cerebellar damage.

Association of Wheat Allergy and Coeliac Disease through Pediatric and Adult Age: A Review of Literature

In recent years, the prevalence of large spectrum of gluten-related disorders (GRDs) has increased. Gluten is one of the most widely distributed components of food in both industrialized and developing countries. The main structural protein complex of wheat and its proteins are classified into albumins, salt-soluble globulins, and insoluble prolamins (gliadins and glutenins). Gluten is also included in other cereals, including rye and barley. GRDs can be classified, based on their pathogenic mechanism, into (i) Autoimmune disorders, (ii) Allergic disorders, (iii) No autoimmune, not allergic disorders. Coeliac disease (CD) is an autoimmune disorder that occurs in genetically predisposed individuals who develop an immune reaction to gluten. It affects about 1% of people in most populations. The disease primarily interests the small intestine, but it is characterized by a wide range of clinical presentations, with both intestinal and extra-intestinal symptoms. Wheat allergy (WA) is an adverse immunologic reaction to wheat proteins. In the large field of WA a further classification can be made, distinguishing IgE-dependent WA, triggered by ingestion, inhalation or cutaneous and/or mucosal contact of wheat, and IgE-non-dependent WA. Its prevalence varies depending on the age and region, from 0.4% to 4%. Urticaria and/or angioedema, and anaphylaxis with or without exercise as a trigger, appear typically during childhood, asthma and/or rhinitis (Baker’s asthma) are more common during adulthood. Non-coeliac gluten sensitivity (NCGS) is a condition in which gluten ingestion leads to one or more of a variety of immunological, morphological or symptomatic (both gastrointestinal or extra gastrointestinal) manifestations in people in whom CD has been excluded. It is supposed it’s due to an activated innate immune response.

NUTRITIONAL AND SENSORY, EVALUATION OF BLENDED FLOUR OF WHITE- MAIZE,BENISEED AND DATE- FRUIT FOR PRODUCTION OF CAKE FOR ACTUALISING SUSTAINABLE DEVELOPMENT GOALS

The study evaluated the sensory and nutritional attributes of blends of white maize and beniseed(Gorigo) flour sweetened with date fruit in cake production. The experimental research design was adopted for the study.Six coded samples of cake produced from wheat, Maize flour, beniseed flour and date fruit: WHS(100%Wheat +Sugar), WHD(100% Wheat +Date), MS(100% Maize+sugar), MD(100% Maize +Date), MBS(50% Maize+50% Beniseed+sugar), MBD(50% Maize+50% Beniseed+Date) were subjected to proximate content dtermination and sensory evaluation. The data obtained were subjected to descriptive and inferential statistics.The result revealed that there was significant difference (p<0.05) in the colour, aroma, taste, texture and overall acceptability of the products, with the sampleWHSbeing most preferred and the sample MD (being least preferred. Sample MBD was least preferred across all sensory quality and overall acceptability.Result of nutritional composition of samples showed that crude protein, moisture, crude fat, crude fibre and ash increased from 7.31 to 11.70, 9.80 to 12.47, 17.26 to 20.17, 2.03 to 2.35, and 1.05 to 1.84 respectively in the maize-beniseed-datesample. However, carbohydrate content reduced from 60.27 in the wheat-date sample to 1.49 in the maize-beniseed-date sample. WHS was most preferred with mean score of 7.73, while sample MDwas least preferred with mean score of 5.40.The study concludes that the maize-beniseed-date sample least preferred across all sensory qualities, the nutritional composition of sample showed that crude protein, moisture, crude fat, crude fibre and ash increased in the maize-beniseed-date sample. It was therefore recommended that the production of maize-beniseed-date sample should be encouraged for its rich source of nutrients, and dietitians should recommend the maize-beniseed-date caketo patients with gluten sensitivity (Celiac patients) and those with protein-energy malnutrition.

Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study.

Goals:This study aimed to understand the neurocognitive symptoms associated with gluten exposure in individuals with self-reported celiac disease (CD) and nonceliac gluten sensitivity (NCGS).Background:While gluten-induced neurocognitive impairment (GINI; eg, “celiac fog” or “brain fog”) is commonly described by individuals with CD and NCGS, there are little data regarding the prevalence and symptoms associated with these experiences.Study:A 9-question online survey was accessed by 1396 individuals (1143 with CD; 253 with NCGS). Forced choice and free-response questions were asked of participants to obtain a description of neurocognitive symptoms experienced after gluten ingestion. Free-response answers were coded using a coding structure developed based on the Health-Related Quality of Life Instrument.Results:The majority of survey participants (89% of CD and 95% of NCGS) reported having GINI symptoms. When describing symptoms, the most common word descriptors for both groups were difficulty concentrating, forgetfulness, and grogginess. Timing of symptoms, including onset and symptom peak, were similar across the 2 groups. Coding of free responses found the most common references were to cognitive, physical, psychological, and overall quality of life impacts.Conclusions:This survey suggests that GINI is common and may be severe in both individuals with CD and NCGS. Cognitive impairment and decline in physical functioning may be similar to that occurring in other illnesses, such as lupus. Clinical follow-up with both individuals with CD and NCGS should include assessment of GINI symptoms. Further research is warranted, including the development of a patient-reported outcome measure including neurocognitive effects of gluten exposure.

P631 Food triggers in inflammatory bowel disease from the patients’ and doctors’ perspective

Abstract Background Diet is receiving growing attention as a key environmental factor involved in the pathogenesis of Inflammatory Bowel Disease (IBD). Dietary components have a relevant role in triggering symptoms from the patients’perspective, but there is a gap between patients’ and doctors’ beliefs. Every patient has collected his or her own list of prohibited foods and reports a clinical benefit from avoiding such foods. Elimination of nutrients can lead to nutritional deficiencies and impact on style and quality of life. The aim of this study is to identify frequently avoided foods in a Mediterranean cohort of patients with IBD. Methods Consecutive patients with IBD attending our tertiary center for infusion of biologics or for follow-up visits were enrolled. Demographics and disease characteristics UC or CD) were recorded in a dedicated database. A questionnaire investigated food avoided and reasons for dietary changes, if self-driven or advised by doctors or other healthcare professionals. Results 167 patients agreed to participate in the study. Eighty-one patients (48.8%) had UC, 86 (51.5%) had CD. Mean age was 48.6 ± 16 (range 18–77 years), 57.5% were males. Patients were in clinical remission or with mild activity. Most patients, about 80%, and especially patients with CD avoided certain foods considered as triggers, and this avoidance was usually practiced in both exacerbations of the disease and remission periods. This occurred upon medical advice in a minority of patients, especially for vegetable avoidance (13.2%). Foods more frequently avoided were spicy foods, seasoned foods, fried foods, milk and dairy products, carbonated drinks, spirits, vegetables, legumes, and whole grain bread. Processed meat was avoided in about 6.6% (only in 1.8% upon medical advice) and coffee in 12.6%. A lactose-free diet was advised by the treating physicians only in 14.3% of patients. 4 patients were on a glutenfree diet because of a self-reported gluten sensitivity. The role of other healthcare professionals (dietitician, nurses) was marginal in their food choices. Conclusion Most of the patients set diet on self-experience and give up many foods. Our results are comparable with those of previous studies. Spicy foods, seasoned and fried foods, carbonated drinks, and dairy products are on top of the list. Legumes and vegetables, the cornerstones of the Mediterranean diet, are also avoided even though the evidence that dietary fibers can induce relapse is lacking. The benefit reported could be related to the effect on IBS-related symptoms frequent in IBD in remission. Further studies and a greater involvement of doctors in providing dietary recommendations are warranted.

Non-Celiac Gluten Sensitivity: An Update.

Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.

Formulation and evaluation of gluten-free cookies from rice and green banana flour

Celiac disease (CD) is defined as an autoimmune pathology mediated by specific antibodies and is associated with genetic factors, which causes an inflammatory process of the intestinal mucosa in response to gluten ingestion. A study was conducted to evaluate some gluten-free cookie formulations using rice and green banana flour as raw material, and to evaluate the acceptance and chemical composition of the cookies elaborated. Three different cookie formulations were prepared to contain 100% rice flour, 50% rice flour and 50% green banana flour and 100% green banana flour. The following sensory attributes were evaluated: crispness, flavor, and overall impression, using the 9-point hedonic scale and purchase intention using the 5-point structured scale, to check the acceptance of cookies. The chemical composition of the formulation most accepted by sensory analysis was quantified. Sensory evaluation showed that all cookie formulations were accepted; however, the increase of the green banana flour content has resulted in lower acceptance, which may be due to the slightly bitter flavor that green banana flour gives the product. The most accepted cookie formulation had 15.78% protein, 0.80% ash, 4.31% moisture content, 12.35% lipid, and 66.77% carbohydrate. These nutritional characteristics are following Brazilian legislation. Therefore, all cookie formulations have marketing potential, which is very important, especially for people with gluten sensitivity.

Long-term Intake of Gluten and Cognitive Function Among US Women

Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease. To examine whether gluten intake is associated with cognitive function in women without celiac disease. This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021. Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment. Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance. The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments. In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.

Awareness of Celiac Disease among the General Public in Saudi Arabia

Background: Celiac disease (CD) is an immune-mediated systemic disorder triggered by dietary gluten and is considered one of the most common lifelong food-related disorders worldwide. The knowledge of CD among the general public in Saudi Arabia remains limited. Therefore, we aimed to assess the awareness and knowledge of CD among the general public in Saudi Arabia. Methods: A cross-sectional online survey including members of the general public was conducted in Saudi Arabia. The survey included questions assessing the public’s awareness about CD, gluten sensitivity, and peanut allergy, as well as celiac disease-related knowledge. Results: From a total of 1230 responses received, 76.7% (95% confidence interval [CI], 74.0%–79.4%) were females, 42.0% (95% CI, 37.7–46.3) were aged between 31–45 years, and 64.3% (95% CI, 61.0%–67.6%) had Bachelor’s degree. Less than half of the participants had heard of CD (48.4%; 95% CI, 44.4%–52.4%), but the majority had heard of peanut allergy (80.1%; 95% CI, 77.6%–82.6%) and gluten sensitivity (72.4%; 95% CI, 69.5%–75.3%). The prevalence of CD was estimated incorrectly by more than 80% of participants. Other questions on participants’ knowledge associated with CD were answered “Do not know” by the majority. Females demonstrated a greater awareness of CD, peanut allergy, and gluten sensitivity, and had a higher percentage of correct responses to questions related to CD than males. Conclusion: This study highlights the need to increase the awareness and knowledge of CD, especially in the recognition of its symptoms. Educational efforts toward increasing the awareness of the general public about CD could help optimize its diagnosis and management.

Emergence of Celiac disease and Gluten-related disorders in Asia.

Celiac disease (CeD) is a systemic, immune-mediated enteropathy, which is triggered by gluten protein in genetically susceptible individuals. CeD, once thought to be an uncommon disease, is now recognized to affect approximately 40-60 million people globally. While CeD is now well reported from a few Asian countries such as India, China, Pakistan, and Middle Eastern countries; it is still believed to be uncommon in the rest of Asia. Gluten-related diseases other than CeD, like non-celiac gluten sensitivity (NCGS) are also emerging globally. CeD and NCGS may present with either intestinal or extra-intestinal symptoms, and a proportion of them have overlapping symptoms with irritable bowel syndrome. Hence, many of them are misdiagnosed as having irritable bowel syndrome in clinical practice. In this review, we discuss the emergence of CeD and other gluten-related disorders, both globally and in Asia, the overlapping manifestations between gluten-related disorders and irritable bowel syndrome, and the challenges associated with diagnosis and management of CeD in Asia.

Glycine receptor antibodies and coeliac disease-related neurological dysfunction

Gluten sensitivity can manifest with a spectrum of neurological dysfunction including ataxia, encephalopathy and neuropathy with or without associated coeliac disease (CD). Gluten sensitivity can also present with central nervous system (CNS) hyperexcitability and cortical myoclonus which is often accompanied with refractory CD. CNS hyperexcitability can also be associated with Glutamic Acid Decarboxylase (GAD) antibodies or much less commonly with Glycine Receptor Antibodies (GlyR-Abs) but the direct pathogenic roles of these antibodies remain debatable. We have previously reported a link between gluten sensitivity and anti-GAD associated ataxia which improves with the adoption of gluten-free diet. It is unclear if a similar link exists between gluten driven CNS hyperexcitability and the presence of GlyR-Abs. We report two cases of CD presenting with CNS hyperexcitability and associated GlyR-Abs. Apart from ataxia and cortical myoclonus, one patient had refractory CD and died from enteropathy-associated T-cell lymphoma. The other patient not only improved with strict gluten-free diet but also showed serological elimination of circulating GlyR-Abs. We conclude that there is an interaction between gluten sensitivity and GlyR-Abs-associated CNS hyperexcitability and in such patients gluten-free diet is an important therapeutic intervention. The elimination of GlyR-Abs by the adoption of gluten free diet suggests that these antibodies may represent an epiphenomenon rather than being directly implicated in the pathogenesis.

FORMULATION OF GLUTEN-FREE BREAD WITH DIFFERENT LEVELS OF HYDROXYPROPYL METHYLCELLULOSE, RAW BANANA FLOUR AND PROOF TIME: MODELLING, PROXIMATE AND SENSORY ANALYSES

Semi-urbanization has increased the demand of bakery products triggering variousgluten-related disorders including Celiac Disease (CD), Non-celiac Gluten Sensitivity (NCGS), Gluten Ataxia and Wheat Allergy. Among these, CD accounts for nearly 1-2%global population. Gluten withdrawal- cornerstone treatment for CD is a bumpy road with nutritional deficiencies and poor quality of life. Additionally, there is a surge of people intentionally avoiding gluten for various reasons. The present work intends to optimize a formula for a gluten free (GF) bread and determine the effect of prooftime, hydroxypropyl methylcellulose (HPMC) and raw banana flour at different levels on moisture content, bake loss, specific volume, texture parameters andcrust-crumb brightness (L*) using response surface methodology (RSM) based on central composite rotatable design (CCRD).The results revealed moisture content, hardness, springiness, resilience and crust-crumb L*were significantly affected. Different proof time levels altered moisture content, bake loss and colour parameters with no influence on textural parameters. Increasing levels of HPMC impeded bake loss and crumb lightness but exacerbated hardness. Nonetheless, on its interaction with raw banana flour, there was antagonistic effect on hardness. Addition of raw banana flour darkened the bread. Thus, optimal conditions (HPMC 2%, raw banana flour 37.16% and proof time 40mins) were appliedto produce good quality bread. Furthermore, sensory and proximateanalyses of optimum GF bread were compared to whole wheat bread depicting higherprotein-fat content, lower carbohydrate content and overall acceptability score of 7.88for the former; the demand for which is steadily and incessantly expanding

Effects of Gliadin on Autoimmune Responses of Central Nervous System of C57BL/6 Mice

Gluten sensitivity contributes to various degrees of neurological manifestations and neurodegenerative immunological changes. We investigated the experimental features of anti-gliadin immune responses in the central nervous system (CNS) of mice. Female C57BL6 mice were divided into three groups. Mice immunized with complete Freund's adjuvant (CFA) or gliadin emulsified in CFA, and the control group received phosphate-buffered saline (PBS). Immunohistochemistry, hematoxylin-eosin, and Luxol fast blue staining were performed on the sections. The serum levels of interleukin (IL)-17 and interferon-gamma (IFN-γ) were measured using enzyme-linked immunosorbent assay (ELISA). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the mRNA levels of chemokine (C-X-C motif) ligand-2 (CXCL-2), C-C motif chemokine ligand-2 (CCL-2), and CXCL-10. In gliadin+CFA immunized mice, the microscopic lesions included perivascular edema, focal-microgliosis, and acute neuronal necrosis in the cortex, subcortical, Purkinje cell layer, and ventral horn of the spinal cord. While extravasation of anti-IgG antibodies and selective targeting of Purkinje cells were observed in gliadin+CFA immunized mice. A significant increase in serum IL-17 and IFN-g levels (p<0.05), as well as expression of CXCL-2, CCL-2, and CXCL-10 in mice immunized with gliadin+CFA, were monitored versus controls. Our findings indicated that the immune responses directed against gliadin peptides mightcontribute to blood-brain barrier breakdown, extravasation of serum anti-IgG, gliosis, and acute neuronal necrosis in the cortex and cerebellar Purkinje cells. Anti-IgG antibodies may cause extravasation of blood-born anti-gliadin antibodies and selective targeting of Purkinje cells observed in mice immunized with peptide tryptic (pt) -gliadin in CFA.

Celiac disease, wheat allergy, and nonceliac sensitivity to gluten: topical issues of the pathogenesis and diagnosis of gluten-associated diseases

Historically, wheat and other gluten-containing grains have been an essential part of the diet of many people worldwide. However, the widespread use of gluten-containing products has led to an increased incidence of adverse reactions associated with their consumption, such as celiac disease and wheat allergy, as well as nonceliac gluten sensitivity, which has become common in recent years.&#x0D; Gluten-associated diseases have similar clinical manifestations (abdominal pain, bloating, diarrhea, nausea, and vomiting). The pathogenetic mechanisms underlying celiac disease and wheat allergy are quite well understood; in both cases, an immune response occurs when wheat proteins are consumed, both with effective treatment. Nonceliac gluten sensitivity is the subject of discussion; however, the processes underlying this disease are not fully understood; thus, its diagnosis and treatment have no unified approach. To date, nonceliac gluten sensitivity is a diagnosis of exclusion, which is established in the absence of markers of celiac disease or wheat allergy and improved following a gluten-free diet.&#x0D; A gluten-free diet is the most effective treatment for gluten-related diseases. However, like any other strict dietary restriction, gluten avoidance can result in reduced intakes of important nutrients, such as dietary fiber, protein, and micronutrients. In recent years, an increasing trend is found in the general population without confirmed gluten-related disorders that gluten-free product consumption or gluten-free diet adherence since gluten avoidance can improve well-being or gluten can be toxic for all human beings&#x0D; According to current guidelines, only patients diagnosed with celiac disease or wheat allergy are advised to follow a strict gluten-free diet.&#x0D; Herein, the modern conception of the immunopathology of gluten-related diseases and an overview of new potential therapies are presented.

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test.

The aims of this observational “proof-of-concept” study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76–0.98, p = 0.021, and OR = 1.30; 95% CI 1.06–1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.

Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated with Gliadin Intake in a Mouse Model of Gluten Sensitivity.

Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, probiotics administration might potentially represent a new valuable strategy to treat gluten-sensitive patients, such as those affected by CD.