Non-celiac Gluten Sensitivity Patients Research Articles

Effect of a Gluten-Free Diet on Whole Gut Transit Time in Celiac Disease (CD) and Non-Celiac Gluten Sensitivity (NCGS) Patients: A Study Using the Wireless Motility Capsule (WMC).

Background: This study explores the impact of a gluten-free diet (GFD) on regional gastrointestinal (GI) transit times in individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). While a GFD is established for managing CD and wheat allergy, its effects on NCGS remain controversial due to inconclusive evidence. Methods: Utilizing a wireless motility and pH capsule (WMC) to assess regional (measurements of gastric, small bowel, and colonic transit times) and whole gut transit, newly diagnosed CD (n = 12) and NCGS (n = 12) patients underwent evaluations at baseline and 4 weeks after having a GFD. Results: At baseline conditions, individuals diagnosed with CD exhibited prolonged colonic and intestinal transit times when compared to those with NCGS (p < 0.05). Following a 4-week GFD, CD patients experienced significant reductions in both intestinal and colonic transit times, along with enhanced small intestine contractility. NCGS individuals showed improvements in intestinal transit time and contractility with a GFD, although the colon exhibited no discernible effect. The GFD did not significantly impact intragastric, intestinal, or colonic pH. Conclusions: This study, employing WMC for the first time, provides novel insights into the positive effects of a GFD on intestinal and colonic transit, as well as contractility, in CD patients, and to a lesser extent, in those with NCGS.

Features of the intestinal microbiome in patients with gluten-sensitive diseases who are on a gluten-free diet

Background. Intestinal dysbiosis is associated with violating both quantitative and qualitative intestinal microbiome (IM) composition. It accompanies different gastrointestinal disorders, including non-celiac gluten sensitivity (NCGS) and celiac disease (CD). A gluten-free diet is the only existing treatment for CD and NCGS. One of the questions of interest is the characteristics of the IM of patients with gluten-related diseases and its relationship with diet therapy. Materials and methods. The study included 25 adults, 14 (56 %) with CD and 11 (44 %) with NCGS; all were on agliadin diet. We determined the faecal content of the Bacteroidetes, Firmicutes, and Actinobacteria and the rest bacterial DNA (“other” indicator) using the real-time polymerase chain reaction. Results. The Bacteroidetes content was 28.4 (Q1-Q3 9.195–37.83) % in CD and 24.98 (Q1-Q3 9.615–30.597) % in NCGS patients, p = 0.565. Firmicutes content was 53.47 (Q1-Q3 49.98–56.798) % in CD patients and 53.0 (Q1-Q3 48.12–68.53) % in NCGS, p = 0.763. The Actinobacteria content was 4.8 (Q1-Q3 3.82–6.84) % in CD patients and 5.37 (Q1-Q3 4.09–7.77) % in NCGS, p = 0.572. There was a moderate positive correlation with the diet duration (p = 0.397, p = 0.03). The Firmicutes/Bacteroidetes ratio was 1.996 (Q1-Q3 1.35–6.85) in CD patients and 2.0 (Q1-Q3 1.65–7.58) in NCGS patients, p = 0.681. The content of “other” types of IM was 15.39 (Q1-Q3 7.44–22.33) % in CD patients and 13.78 (Q1-Q3 10.65–15.58) % in NCGS patients, p = 0.936. Conclusions. We found similar intestinal microbiome features in patients with celiac disease and non-celiac gluten sensitivity. The detected intestinal microbiome changes are most likely to be a consequence of dietary features in such patients, namely the side effect of maintaining an agliadin diet.

Contribution of the Leukocyte Adherence Inhibition Test for the Evaluation of Immunoreactivity against Gluten Extracts in Non—IgE-Mediated / Non-Autoimmune Gluten-Related Disorders

Background: The Non-Celiac Gluten Sensitivity (NCGS) is a category inside the Gluten-Related Disorders (GRD) that groups the patients with unidentified mechanisms responsible for their symptoms.&#x0D; Objective: To evaluate the opportunity of an ex vivo challenge immunoassay, the Leukocyte Adherence Inhibition Test (LAIT), to discriminate non—IgE-mediated gluten-specific immunoreactivity in patients with NCGS.&#x0D; Methods: Ex vivo challenge tests performed with gluten latex extract, monitored by LAIT, were assayed in an asymptomatic control group of 30 individuals and a group of 52 patients with GRD not related to any identifiable immune mechanism (NCGS).&#x0D; Results: The mean Leukocyte Adherence Inhibition (LAI) of the control group was 10.9%. The mean LAI of the NCGS patients’ group was 54.9%. The non-parametric Wilcoxon-Mann-Whitney U test comparing the control group with the NCGS patient’s group showed significance with a p-value &lt; 0.00001.&#x0D; Conclusion: The LAIT is an ex vivo challenge test able to discriminate gluten-sensitive and gluten-tolerant individuals, suggesting the participation of an immune Non—IgE-mediated hypersensitivity reaction in patients with the clinical diagnosis of NCGS.

Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet.

PurposeMarkers for gut integrity and inflammation have received increasing interest as intestinal permeability and innate immune system activation are suggested as possible pathophysiological mechanisms in non-celiac gluten sensitivity (NCGS). We aimed to assess relevant biomarkers in NCGS by analyzing serum levels of gut integrity and permeability markers, pro-inflammatory cytokines and antigliadin IgG in patients with suspected NCGS on a gluten-free diet (GFD), and compare them to serum levels in patients with irritable bowel syndrome (IBS) and healthy controls (HC).Patients and MethodsSerum samples collected from patients with suspected NCGS on a GFD (n=20, 14 women, 21–62 years), IBS (n=20, 16 women, 24–67 years) and HC (n=20, 14 women, 21–54 years) were analyzed. IBS severity scoring system (IBS-SSS) was applied to evaluate gastrointestinal symptoms.ResultsThe IBS-SSS score was higher in subjects with suspected NCGS and IBS patients compared to HC (p<0.0001). No significant differences were found in the serum levels of any of the gut integrity and permeability markers, cytokines or antigliadin IgG antibodies between the three groups. However, positive correlations were observed between claudin-1 and i-FABP, and between claudin-1 and antigliadin IgG antibodies.ConclusionNo differences in serum levels of gut integrity and permeability markers, pro-inflammatory cytokines or antigliadin IgG antibodies were found among patients with suspected NCGS on a GFD, IBS and HC.

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.

Prevalence of Non-Celiac Gluten Sensitivity in Patients with Refractory Functional Dyspepsia: a Randomized Double-blind Placebo Controlled Trial

Refractory functional dyspepsia (RFD) is characterized by symptoms persistence in spite of medical treatment or H. pylori eradication. No study has yet investigated the presence of gluten-dependent RFD as a clinical presentation of Non-Celiac Gluten Sensitivity (NCGS). Patients with RFD, in whom celiac disease, wheat allergy and H. pylori infection had been ruled out, followed a six weeks long gluten-free diet (GFD). Symptoms were evaluated by means of visual analogue scales; patients with ≥30% improvement in at least one of the reported symptoms after GFD underwent a double-blind placebo controlled gluten challenge. Subjects were randomly divided in two groups and symptoms were evaluated after the gluten/placebo challenge. GFD responders were further followed on for 3 months to evaluate the relationship between symptoms and gluten consumption. Out of 77 patients with RFD, 50 (65%) did not respond to GFD; 27 (35%) cases showed gastrointestinal symptoms improvement while on GFD; after blind gluten ingestion, symptoms recurred in 5 cases (6.4% of patients with RFD, 18% of GFD responders) suggesting the presence of NCGS. Furthermore, such extra-intestinal symptoms as fatigue and weakness (P = 0.000), musculo-skeletal pain (P = 0.000) and headache (P = 0.002) improved in NCGS patients on GFD. Because of the high prevalence of NCGS among patients with RFD, a diagnostic/therapeutic roadmap evaluating the effect of GFD in patients with RFD seems a reasonable (and simple) approach.

Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them.

Wheat is a major cereal crop providing energy and nutrients to the billions of people around the world. Gluten is a structural protein in wheat, that is necessary for its dough making properties, but it is responsible for imparting certain intolerances among some individuals, which are part of this review. Most important among these intolerances is celiac disease, that is gluten triggered T-cell mediated autoimmune enteropathy and results in villous atrophy, inflammation and damage to intestinal lining in genetically liable individuals containing human leukocyte antigen DQ2/DQ8 molecules on antigen presenting cells. Celiac disease occurs due to presence of celiac disease eliciting epitopes in gluten, particularly highly immunogenic alpha-gliadins. Another gluten related disorder is non-celiac gluten-sensitivity in which innate immune-response occurs in patients along with gastrointestinal and non-gastrointestinal symptoms, that disappear upon removal of gluten from the diet. In wheat allergy, either IgE or non-IgE mediated immune response occurs in individuals after inhalation or ingestion of wheat. Following a life-long gluten-free diet by celiac disease and non-celiac gluten-sensitivity patients is very challenging as none of wheat cultivar or related species stands safe for consumption. Hence, different molecular biology, genetic engineering, breeding, microbial, enzymatic, and chemical strategies have been worked upon to reduce the celiac disease epitopes and the gluten content in wheat. Currently, only 8.4% of total population is affected by wheat-related issues, while rest of population remains safe and should not remove wheat from the diet, based on false media coverage.

Microbial production of essential and toxic compounds among oat-using CeD and NCGS patients

AbstractThe recent development of diagnostic methods and current well-being trend have increased the awareness of gluten-related diseases, such as celiac disease (CeD) and non-celiac gluten sensitivity (NCGS), 1% and 6 % of general population, respectively. Currently for both CeD and NCGS, the only effective treatment is a life-long gluten-free diet, which makes adequate intake of fiber challenging. Despite of improving gut function, dietary fibers promote the growth of gut beneficial microbes. They are in charge of production of numerous compounds, which are essential for human health, such as enzymes and short chain fatty acids (SCFA). Moreover, dietary fiber has an effect on ammoniacal nitrogen levels and beta-glucuronidase activity, which are harmful for human in high concentrations. Gluten-free oats are an excellent source of dietary fiber and they have exceptionally good nutritional properties.In this observational study, SCFA production, ammoniacal nitrogen levels and beta-glucuronidase activity of oat-using CeD patients, NCGS patients and healthy controls were compared. SPME-GC-MS method was developed for SCFA analysis and the other biomarkers were analyzed by spectrophotometer.There were no significant differences between groups on propionic acid and butyric acid production, only the percentage of acetic acid of total SCFAs was higher in control group compared to NCGS group, (p = 0,03). Neither was there significant differences between groups in ammonia production or beta-glucuronidase activity.It has been scientifically proven that pure oats are suitable for celiac disease and gluten-sensitive patients, but they are not commonly used outside of Scandinavia. Our results stated that oat-using CeD and NCGS patients, whose disease is in balance, have gut microbiota capable of healthy production of essential SCFAs and normal levels of harmful compounds.

Immunoreactivity of Gluten-Sensitized Sera Toward Wheat, Rice, Corn, and Amaranth Flour Proteins Treated With Microbial Transglutaminase.

The aim of this study was to analyze the effects of microbial transglutaminase (mTG) on the immunoreactivity of wheat and gluten-free cereals flours to the sera of patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). Both doughs and sourdoughs, the latter prepared by a two-step fermentation with Lactobacillus sanfranciscensis and Candida milleri, were studied. In order to evaluate the IgG-binding capacity toward the proteins of the studied flours, total protein as well as protein fractions enriched in albumins/globulins, prolamins and glutelins, were analyzed by SDS-PAGE and enzyme-linked immunosorbent assay (ELISA). Results showed that while mTG modified both gluten and gluten-free flour by increasing the amount of cross-linked proteins, it did not affect the serum's immune-recognition. In fact, no significant differences were observed in the immunoreactivity of sera from CD and NCGS patients toward wheat and gluten-free protein extracts after enzyme treatment, nor did this biotechnological treatment affect the immunoreactivity of control samples or the sera of healthy patients. These results suggest that mTG may be used as a tool to create innovative gluten and gluten-free products with improved structural properties, without increasing the immune-reactivity toward proteins present either in doughs or in sourdoughs.

Predictivity of Autoimmune Stigmata for Gluten Sensitivity in Subjects with Microscopic Enteritis: A Retrospective Study

Non-celiac gluten sensitivity (NCGS) is an emerging gluten-related condition. We investigated whether the presence of autoimmune stigmata in a group of patients with clinical suspicion of NCGS and a histological picture of microscopic enteritis (ME) could be a predictive factor of NCGS. Patients with ME were followed up by periodical examinations. At baseline, we collected data about previous clinical history, including autoimmune diseases. NCGS was diagnosed according to Salerno criteria; other causes of ME were diagnosed according to well-established protocols. Patients with celiac disease were excluded. Student’s and chi-square tests were used in univariate analysis. Kaplan-Meier curves and Cox regression were used to estimate hazard ratios (HR). Sixty-three patients were included. Twenty-two had a final diagnosis of NCGS; the remaining 41 had non-gluten-related causes of ME. Prevalence of autoimmune thyroiditis was higher among NCGS patients (40.1%) than in other ME (14.6%; p = 0.03). NCGS showed higher positivity rate for anti-gliadin (27.3% versus 2.5%; p = 0.006) and anti-nucleus (45.4% versus 12.2%; p = 0.005). Autoimmune thyroiditis had a non-significant trend (p = 0.06) for NCGS diagnosis, (HR = 2.4). Both anti-gliadin (HR = 2.4; p = 0.04) and anti-nucleus (HR = 2.7; p = 0.04) were directly associated with NCGS diagnosis. In conclusion, NCGS may have a cohort of autoimmune stigmata that can precede its diagnosis.

Motility Disorders in Celiac Disease and Non-Celiac Gluten Sensitivity: The Impact of a Gluten-Free Diet.

Background: There is evidence that digestive motor disorders are frequently present in untreated celiac disease (CD) patients. Similarly, non-celiac gluten sensitivity (NCGS) can be associated with gut motor disorders. In both cases, gut dysmotility can improve or be completely reversed with a gluten-free diet (GFD). Methods: A literature search for motility disorders in CD and NCGS patients was carried out using the online databases PubMed, Medline and Cochrane. Results: Esophageal, gastric, small bowel and gallbladder motor disorders are common in both children and adults with CD. Although the clinical consequences of these disorders are not clearly defined, gastric dysfunction could affect drug absorption and metabolism in the thyroid and neurological conditions associated with CD. The impact of a GFD on motility disorders is, however, controversial. No systematic studies are available on NCGS. NCGS frequently overlaps with irritable bowel syndrome (IBS) and similar pathophysiological mechanisms may be hypothesized. Conclusions: Mucosal damage may affect gut motility in untreated CD through perturbation of hormonal and neuro-immunomodulatory regulation. A persistent low-grade mucosal inflammation could explain the cases of persistent motor disorders despite a GFD. Further studies are needed to definitely assess the role of gut motor disorders in NCGS.

Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm.

Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind’, headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Influence of low FODMAP and gluten-free diets on disease activity and intestinal microbiota in patients with non-celiac gluten sensitivity

Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms triggered by ingestion of gluten. However, non-gluten triggers have recently been implicated, and a FODMAP (fermentable oligo-, di-, monosaccharides and polyols)-reduced diet can partially improve symptoms in NCGS. Our aim was to analyze the effect of a low FODMAP versus a gluten-free diet (GFD) on clinical symptoms, psychological well-being, intestinal inflammation and integrity, and stool microbiota. Nineteen patients with NCGS and ten healthy controls consumed a gluten-containing standard diet before starting a two-week low FODMAP diet; after a five day transition period, participants ingested a GFD for another two weeks. The primary outcome measure was the improvement of clinical symptoms in NCGS patients under the different diets. Secondary outcomes were the determination of dietary effects on intestinal inflammation, psychological well-being, and differences in stool microbiota between NCGS patients and controls. The low FODMAP diet and especially the GFD led to a significant improvement of clinical and psychological symptoms in NCGS. A clear reduction in duodenal intraepithelial lymphocytes and mucin-producing Goblet cells was found after the GFD in these patients. Significant microbial differences between NCGS patients and controls were noticed in stool samples at every time point. Both diets caused microbial shifts in all participants, with a greater variability on genus level and metabolisms groups in NCGS patients. Our findings suggest a multifactorial etiology of NCGS, due to a functional effect caused by FODMAPs, combined with a mild gluten-triggered immune reaction, and a microbiota dysbalance. CLINICALTRIAL. NCT03268720.

Amylase-Trypsin Inhibitors in Wheat and Other Cereals as Potential Activators of the Effects of Nonceliac Gluten Sensitivity.

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

Cerebellar Ataxia, Celiac Disease and Non-Celiac Gluten Sensitivity

: Cerebellar ataxia (CA) is one of the most frequent neurological manifestations related to celiac disease (CD). Celiac disease is found in patients with a percentage ranging from 1.9% to 16.7%. Gluten cerebellar ataxia is purely cerebellar and involves the entire cerebellum. The clinical signs of CA are gait ataxia, limb ataxia, dysarthria, pyramidal signs, altered eyes motions, and progressive impairment of stability, and erect position. The patients affected by Gluten CA show an immunological response against a primarily brain expressed TG, such as TG6. The prolonged gluten consumption in patients with gluten ataxia leads to a progressive loss of purkinje cells in the cerebellum. An early diagnosis of CA and gluten related disorders (GRD) increases the possibility to improve the neurological process. Non celiac gluten sensitivity (NCGS) is defined by clinical evidence of improvement of symptoms following the introduction of GFD in the absence of enteropathy. The increased recognition of the whole spectrum of Gluten related disorders (GRD) is the best way to improve the time of the diagnosis and to avoid patients with neurological manifestation remaining untreated if duodenal biopsy does not reveal an enteropathy. Cerebellar Ataxia is equally responsive to GFD in CD and NCGS patients.

Responses of blood mononucleated cells and clinical outcome of non-celiac gluten sensitive pediatric patients to various cereal sources: a pilot study

Non-celiac gluten sensitivity (NCGS) is a clinical entity recently documented by the scientific community in pediatric patients. Nevertheless, its triggering mechanisms remain largely unsettled. We studied 11 children with NCGS who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, matched with 18 children with active CD. Sixteen pediatric patients were also enrolled as controls. Cultured peripheral blood mononucleated cells (PBMCs) obtained from NCGS, CD and control patients were cultured in the presence of wheat proteins extracted from ancient and modern cultivars. Results demonstrated that wheat proteins induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS pediatric patients and that this overexpression also depended on the wheat cultivar from which proteins were extracted. Proteins from modern wheat cultivar activated CXCL10 to a greater extent than those extracted from ancient wheat genotypes.

Symptomatic efficacy of buckwheat products in Non-Celiac Gluten Sensitivity (NCGS).

Buckwheat (Fagopyrum esculentum) is a gluten-free grain with acclaimed benefi-cial effects on human health. Our aim was to assess the effect of buckwheat products on intestinal/extra-intestinal symptoms and biochemical parameters in patients with Non-Celiac Gluten Sensitivity (NCGS). A randomized, crossover trial with two intervention phases was conducted on 19 NCGS patients over a 12 week-period. The participants were assigned to consume products made from buckwheat or to maintain their normal gluten-free diet for 6 weeks in a random order. Symptoms due to NCGS were evaluated using two questionnaires. During the intervention period with buckwheat products, patients experienced a signifi-cant decrease in the severity of abdominal pain and bloating (p=0.03). In contrast, the control group showed a significant worsening trend for the majority of NCGS symptoms such as nausea, headache, joint/muscle pain, and attention disorders. The replacement diet with buckwheat products also resulted in a significant increase of serum magnesium (+4.7%) and a significant reduction in the circulating levels of some pro-inflammatory cytokines such as interferon gamma (-33.3%) and monocyte chemotactic protein-1 (-46.5%). The study supports the positive effects of buckwheat for NCGS patients, showing that this alternative cereal can contribute to the re-duction of both negative gastro-intestinal and related symptoms, and nutritional deficiencies, and lead to an im-provement in inflammatory profile.

Anti-gliadin antibodies in non-celiac gluten sensitivity.

Although no biomarker has been identified to date, previous studies have reported that about 50% of patients with suspected non-celiac gluten sensitivity (NCGS) had positive first generation anti-gliadin antibodies (AGAs), especially of the IgG class. These antibodies are not specific for NCGS, being also found in CD (80-90%), autoimmune liver disorders (21.5%), connective tissue disease (9%) and IBS (20%), as well as in healthy controls (2-8%), but their finding in patients with a clinical phenotype consistent with NCGS has been regarded as an element supporting this diagnosis. Even though the correlation between AGA IgG and NCGS condition turned out to be statistically significant in most studies, AGA IgG does not seem to be an adequately strong marker for its lacking diagnostic accuracy. However it can partly help the NCGS diagnosis, integrated in the overall management of the patient. Therefore, in the presence of clinical symptoms that suggest NCGS, IgG AGA positivity, together with negative anti-tTG, EMA, and anti-deamidated-gliadin-peptides (DGP) antibodies, NCGS diagnosis might be suspected. Future researches are necessary to identify reliable biomarkers for NGCS diagnosis and to better define clinically and serologically NCGS patients.

Intestinal, Systemic, and Oral Gluten-related Alterations in Patients With Nonceliac Gluten Sensitivity.

Nonceliac gluten sensitivity (NCGS) is an emergent condition, the framework of which is yet unclear, whereas the diagnosis is suggested only by gluten-dependent symptoms after excluding wheat allergy and celiac disease (CD). Our goal was to highlight intestinal, systemic, and oral alterations to clarify the NCGS pathogenesis and identify new diagnostic tools. A total of 60 NCGS patients, 20 untreated CD, 20 treated CD, and 20 healthy volunteers were recruited. The differential diagnosis among gluten-related disorders was performed by serological, allergy, and histologic tools. NCGS patients were also subjected to antigliadin antibody (AGA) detection and HLA typing. All participants underwent an oral mucosa patch test for gluten (GOMPT), whereas an oral provocation test (OPT) for gluten was performed in 26 NCGS patients. About 6/60 (10%) NCGS patients showed IgG AGA-positive results, whereas 45/60 (75%) patients carried HLA-DQ2 and/or HLA-DQ8 genes. GOMPT showed positive results in 45/60 (75%) NCGS patients, 3/20 (15%) untreated CD patients, 5/20 (25%) treated CD patients, and in no healthy volunteers. No significant difference was found between the severity of symptoms reported by NCGS patients subjected to OPT with gluten-containing croissants and those who underwent OPT with gluten-free croissants. GOMPT seems to be a specific tool for NCGS diagnosis, although further investigations are needed to overcome limits due to the small population studied and to contextualize GOMPT false-positive results.

Suspected Nonceliac Gluten Sensitivity Confirmed in FewPatients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies.