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Reizdarm, Zöliakie, Weizenallergie, Weizensensitivität – die Schwierigkeit, die Spreu vom Weizen zu trennen

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Abstract

Zusammenfassung Ernährungsfaktoren spielen eine wichtige Rolle bei Auslösung und Verschlimmerung von Bauchschmerzen, Blähungen und Durchfall bei Patienten mit Reizdarmsyndrom (RDS). Seit Abgrenzung eines neuen Krankheitsbildes zwischen RDS und Zöliakie, der non-celiac gluten sensitivity/Weizensensitivität, und seit Erscheinen eines in Laienkreisen viel beachteten Bestsellers zu negativen gesundheitlichen Effekten von Weizen, hat eine glutenfreie Ernährung seit einigen Jahren erheblich an Popularität zugenommen. In einer Übersicht werden die Unterschiede zwischen RDS, Zöliakie, Weizenallergie und Weizensensitivität dargestellt und Studien, die den Weizenbestandteilen Gluten oder Fruktanen/FODMAPs (fermentierbaren Oligo-, Di-, Monosacchariden und Polyolen) eine auslösende Rolle zusprechen, erörtert. Vor- und Nachteile einer glutenfreien Diät und FODMAP-armen Ernährung werden diskutiert. Abschließend wird erläutert, bei welchem Patienten zu einer glutenfreien Ernährung und bei welchem Patienten zu einer FODMAP-armen Ernährung geraten werden sollte.

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Zusammenfassung Eine glutenfreie Ernährung ist seit 60 Jahren die einzige Therapieoption für Patienten mit Zöliakie oder Dermatitis herpetiformis zur Normalisierung der Beschwerden und Verhinderung von Komplikationen. Eine glutenfreie Ernährung erfreut sich jedoch in jüngster Zeit zunehmender Beliebtheit wegen vermuteter Effekte auf Wohlbefinden und Leistungsfähigkeit sowie zur Kontrolle des Körpergewichts. In der vorliegenden Übersicht wird auf gesicherte Indikationen für eine glutenfreie Ernährung, auf die Notwendigkeit einer eingehenden Beratung und Schulung des Patienten, auf Probleme und Schwierigkeiten bei der Umsetzung einer glutenfreien Ernährung in den täglichen Alltag und auf mögliche Nebenwirkungen unter Langzeittherapie eingegangen. Neue Methoden zur Überprüfung der Adhärenz zu einer glutenfreien Ernährung werden erörtert, die ernährungsmedizinische Qualität etlicher lebensmitteltechnologisch hergestellter glutenfreier Nahrungsmittel wird kritisch diskutiert.
Article
Dietary intake of fermentable oligo-, di- and monosaccharides, and polyols (FODMAP) has previously been shown to aggravate the symptoms of the irritable bowel syndrome (IBS), furthermore being associated with wheat sensitivity and a bread wheat-specific intolerance. FODMAP in whole grain flours and breads made of different varieties of bread wheat, spelt, durum, emmer, and einkorn were determined by high-performance anion exchange chromatography with pulsed amperometric detection. Fructans and raffinose were the only FODMAP detected in wheat flour. Total FODMAP contents ranged from 1.24±0.38 to 2.01±0.42g/100g DM in emmer and einkorn flours, respectively. During bread making, prolonging dough proofing times (>4 hours) allowed to effectively diminish FODMAP levels of the final product by up to 90%. Therefore, the applied processing method was substantially more important than the selection of the used variety in order to obtain low-FODMAP wheat bakery products, suitable for consumption by IBS patients.
Article
Objectives: Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD. Methods: Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects. Results: Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC. Conclusions: Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.Am J Gastroenterol advance online publication, 17 May 2016; doi:10.1038/ajg.2016.162.
Article
Background & aims: The only available treatment for celiac disease (CD) is lifelong adherence to gluten free (GF)-diet. However, GF-diet may lead to possible nutrient unbalance resulting in improper nutritional quality of diet. The aim of this study is to evaluate the nutritional quality of GF-diet. Methods: MEDLINE(®)/PubMed and Cochrane Library were electronically searched for articles published between 1990/01/01 and 2015/09/01. Results: GF-diet was found to be poor in alimentary fiber due in particular to the necessary avoidance of several kinds of foods naturally rich in fiber (i.e. grain) and the low content of fiber of GF product that are usually made with starches and/or refined flours. Micronutrients are also found to be poor, in particular Vit. D, Vit. B12 and folate, in addition to some minerals such as iron, zinc, magnesium and calcium. Moreover, an inadequate macronutrient intake was reported related above all to the focus on the avoidance of gluten that often leaving back the importance of nutritional quality of the choice. In particular, it was found a higher content of both saturated and hydrogenated fatty acids and an increase in the glycemic index and glycemic load of the meal. Conclusions: Despite the GF-diet is necessary in celiac disease treatment and the attention is on gluten avoidance, the evaluation of nutritional quality of the diet must be considered. Moreover, educational strategies based on the relationship between nutrients and food and human health could be developed to optimize the therapeutic approach in celiac patients.
Chapter
Celiac disease (CD) is a model for common complex disorders with a high degree of heritability. The human leukocyte antigen (HLA) DQ genotype, specifically HLA-DQ2 and HLA-DQ8, is the strongest genetic risk factor. Genome-wide association studies (GWAS) have identified 57 single nucleotide polymorphisms (SNPs) located in the associated 39 non-HLA regions with mainly immunological functions. Together with HLA, these regions explain approximately 54 % of the disease’s heritability. Molecular functional analyses are necessary to delineate the true causal genetic variants and the pathways involved. Since CD shares many of its genetic susceptibility regions and implicated pathways with other immune-related diseases, a combined analysis may discover more common genetic variants with smaller effect sizes. HLA-DQ genotyping can already be used to exclude a diagnosis of CD, for example, as a test in the screening of individuals from high-risk groups, such as patients with type 1 diabetes or autoimmune thyroiditis, and first-degree relatives of CD patients. Discovering more genetic susceptibility variants and the pathways involved may ultimately contribute to risk stratification for follow-up and treatment, and lead to new therapeutic targets.
Chapter
Over the last 25 years, with the concerted effort of many researchers, we have learned a lot about the pathophysiology of celiac disease (CD). Now, CD is the best understood autoimmune/immune-mediated illness. This chapter will discuss current understanding of gluten as an antigen, antigen-presentation, and the role of HLA-DQ2/DQ8, how gluten peptides cross the intestinal epithelial cell barrier, the importance of tissue transglutaminase for modifying gluten peptides for presentation, the role of intestinal T cells in coordinating inflammation, how intraepithelial lymphocytes are triggered to attack intestinal epithelial cells, and the role of antibody response.
Article
Purpose of review: This article evaluates the current status of the gut barrier in gastrointestinal disorders. Recent findings: The gut barrier is a complex, multicomponent, interactive, and bidirectional entity that includes, but is not restricted to, the epithelial cell layer. Intestinal permeability, the phenomenon most readily and commonly studied, reflects just one (albeit an important one) function of the barrier that is intimately related to and interacts with luminal contents, including the microbiota. The mucosal immune response also influences barrier integrity; effects of inflammation per se must be accounted for in the interpretation of permeability studies in disease states. Summary: Although several aspects of barrier function can be assessed in man, one must be aware of exactly what a given test measures, as well as of its limitations. The temptation to employ results from a test of paracellular flux to imply a role for barrier dysfunction in disorders thought to be based on bacterial or macromolecular translocation must be resisted. Although changes in barrier function have been described in several gastrointestinal disorders, their primacy remains to be defined. At present, few studies support efficacy for an intervention that improves barrier function in altering the natural history of a disease process.
Article
Celiac Disease and Gluten: Multidisciplinary Challenges and Opportunities is a unique reference work-the first to integrate the insights of the causes and effects of celiac disease from the chemistry of reaction-causing foods to the diagnosis, pathogenesis, and symptoms that lead to proper diagnoses and treatment. With an estimated three million people in the United States alone affected by celiac disease, an autoimmune digestive disease, only five percent are properly diagnosed. Drawing on the connection between foods containing gluten and the resulting symptoms, this resource offers distinctive information that directly explores and links food science, medical diagnostics, and treatment information. A helpful tool for researchers and medical practitioners alike, Celiac Disease and Gluten: Multidisciplinary Challenges and Opportunities helps refine research targets, and provides a comprehensive overview on the multidisciplinary approaches to all crucial aspects related to celiac disease. • Presents key information from medical and food science research, as well as provides clinical insights • Provides direct corollary insights between source and symptom • Written by experts whose detailed experiments and results have shaped our understanding of celiac disease.
Article
Background/objectives: Adherence to gluten-free diet in self reported non-coeliac gluten sensitive subjects is scarcely researched. Objectives of the study were to compare dietary adherence in coeliac disease (CD) subjects and in non-coeliac gluten sensitive (NCGS) subjects, and to estimate gluten exposure based on weighed food records and analysis of gluten content in selected food items. Subjects/methods: Twenty-three subjects with biopsy verified CD on a gluten-free diet and 34 HLA-DQ2(+) NCGS subjects on a self-instituted gluten-free diet were enrolled. The latter group was under investigation of CD. Dietary adherence was assessed by frequency questionnaire and structured forms supplied by weighed food records. For the analyses of food samples, the sandwich R5-ELISA, Ridascreen(®) Gliadin competitive method was used. Results: There was no difference in dietary adherence between CD and NCGS subjects (83% vs 68%, p = 0.21). NCGS subjects were mainly self-educated in gluten-free diet compared to CD subjects (91% and 39%, respectively, p < 0.001). In non-adherent subjects, there was no difference in gluten exposure between CD and NCGS (10 vs 138 mg/day, p = 0.83). There was no difference in BMR-factor between CD and NCGS subjects, or between adherent and non-adherent subjects. Conclusions: Both CD and NCGS subjects were largely adherent, and adherence did not differ between the groups. Gluten exposure varied greatly, and some CD and NCGS subjects reached gluten intake above 500 mg/day, which might have considerable health effects on the individual, especially in case of coeliac disease.
Article
It is unknown whether symptoms in non-coeliac patients (non-CD) meeting clinical diagnostic criteria for noncoeliac gluten sensitivity (NCGS) are specifically triggered by gluten. To assess gluten sensitivity in patients diagnosed with NCGS. We studied 35 non-CD subjects (31 females) that were on a gluten-free diet (GFD), in a double-blind challenge study. Participants were randomised to receive either gluten-containing flour or gluten-free flour for 10 days, followed by a 2-week washout period and were then crossed over. The main outcome measure was their ability to identify which flour contained gluten. Secondary outcome measures were based upon Gastrointestinal Symptoms Rating Scale (GSRS) scores. The gluten-containing flour was correctly identified by 12 participants (34%), who were classified as having NCGS. Their mean GSRS dimension scores were significantly higher following gluten challenge compared to baseline. The scores were: pain, 1.7 ± 0.8 vs. 2.6 ± 1.0; reflux, 1.6 ± 0.5 vs. 2.2 ± 0.9; indigestion, 1.9 ± 0.7 vs. 3.2 ± 1.1; diarrhoea, 1.6 ± 0.7 vs. 2.9 ± 1.5 and constipation, 1.9 ± 0.9 vs. 2.9 ± 1.3. Seventeen participants (49%) erroneously considered the gluten-free flour to contain gluten. Their mean GSRS dimension scores were significantly higher following gluten-free flour challenge compared to baseline. The scores were: pain, 1.6 ± 0.9 vs. 3.0 ± 0.9; reflux, 1.4 ± 0.5 vs. 2.3 ± 1.1; indigestion, 2.0 ± 1.1 vs. 3.7 ± 1.1; diarrhoea, 1.6 ± 0.7 vs. 3.0 ± 1.2 and constipation, 1.6 ± 0.9 vs. 2.6 ± 1.3. The other six participants (17%) were unable to distinguish between the flours. Double-blind gluten challenge induces symptom recurrence in just one-third of patients fulfilling the clinical diagnostic criteria for non-coeliac gluten sensitivity. © 2015 John Wiley & Sons Ltd.
Article
IBS is one of the most common types of functional bowel disorder. Increasing attention has been paid to the causative role of food in IBS. Food ingestion precipitates or exacerbates symptoms, such as abdominal pain and bloating in patients with IBS through different hypothesised mechanisms including immune and mast cell activation, mechanoreceptor stimulation and chemosensory activation. Wheat is regarded as one of the most relevant IBS triggers, although which component(s) of this cereal is/are involved remain(s) unknown. Gluten, other wheat proteins, for example, amylase-trypsin inhibitors, and fructans (the latter belonging to fermentable oligo-di-mono-saccharides and polyols (FODMAPs)), have been identified as possible factors for symptom generation/exacerbation. This uncertainty on the true culprit(s) opened a scenario of semantic definitions favoured by the discordant results of double-blind placebo-controlled trials, which have generated various terms ranging from non-coeliac gluten sensitivity to the broader one of non-coeliac wheat or wheat protein sensitivity or, even, FODMAP sensitivity. The role of FODMAPs in eliciting the clinical picture of IBS goes further since these short-chain carbohydrates are found in many other dietary components, including vegetables and fruits. In this review, we assessed current literature in order to unravel whether gluten/wheat/FODMAP sensitivity represent 'facts' and not 'fiction' in IBS symptoms. This knowledge is expected to promote standardisation in dietary strategies (gluten/wheat-free and low FODMAP) as effective measures for the management of IBS symptoms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Article
There is much interest in wheat sensitivity among people without celiac disease (NCWS), but little is known about any risks associated with the condition. We evaluated the prevalence of autoimmune diseases among patients with NCWS, and investigated whether they carry anti-nuclear antibodies (ANA). We performed a retrospective study of 131 patients diagnosed with NCWS (121 female; mean age, 29.1 y) at 2 hospitals in Italy from January 2001 through June 2011. Data were also collected from 151 patients with celiac disease or irritable bowel syndrome (IBS) (controls). Patients' medical records were reviewed to identify those with autoimmune diseases. We also performed a prospective study of 42 patients (38 female; mean age, 34 y) diagnosed with NCWS from July 2011 through March 2014 at 3 hospitals in Italy. One hundred age- and sex-matched subjects with celiac disease or IBS served as controls. Serum samples were collected from all subjects and ANA levels were measured by immunofluorescence analysis. Participants completed a questionnaire and their medical records were reviewed to identify those with autoimmune diseases. In the retrospective analysis, similar portions of subjects with NCWS (29%) and celiac disease (29%) developed autoimmune diseases (mainly Hashimoto's thyroiditis, 29 cases), compared with a smaller proportion of subjects with IBS (4%) (P<.001). In the prospective study, 24% of subjects with NCWS, 20% if subjects with celiac disease, and 2% subjects with IBS developed autoimmune diseases (P<.001). In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS (median titer 1:80), 24% of subjects with celiac disease (P<.001), and 2% of subjects IBS (P<.001); in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with celiac disease (P=.02), and 6% of subjects with IBS (P=.005 vs patients with NCWS). ANA positivity was associated with the presence of the HLA DQ2/DQ8 haplotypes (P<.001). Higher proportions of patients with NCWS or celiac disease develop autoimmune disorders, are ANA positive, and showed DQ2/DQ8 haplotypes compared to patients with IBS. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Article
Implementation of gluten-free diets amongst non-celiac athletes has rapidly increased in recent years due to perceived ergogenic and health benefits. The aim of this study was to investigate the effects of a gluten-free diet (GFD) on exercise performance, gastrointestinal (GI) symptoms, perceived well-being, intestinal injury, and inflammatory responses in non-celiac athletes. Thirteen competitive endurance cyclists (8 males, 5 females) with no positive clinical screening for celiac disease or history of irritable bowel syndrome (mean±SD; age: 32±7 years; weight: 71.1±13.4kg; height 177.0±11.8cm, VO2max 59.1±8.0ml.kgmin) were allocated to a seven day gluten-containing diet (GCD) or GFD separated by a 10-day washout in a controlled randomized double-blind, cross-over study. Cyclists ate a GFD alongside either gluten-containing or gluten-free food bars (16g wheat gluten per day) while habitual training and nutrition behaviors were controlled. During each diet, cyclists completed the Daily Analysis of Life Demand for Athletes (DALDA) and GI questionnaires (post-exercise and daily). On day seven cyclists completed a submaximal steady-state (SS) 45 minute ride at 70% peak power followed by a 15 minute time-trial (TT). Blood samples were taken pre-exercise, post SS and post TT to determine intestinal fatty acid binding protein (IFABP) and inflammatory markers (cytokine responses: IL-1β, IL-6, IL-8, IL-10, IL-15, TNF-α). Mixed effect logistic regression was used to analyze data. TT performance was not significantly different (p=0.37) between the GCD (245.4±53.4kJ) and GFD (245.0±54.6kJ). GI symptoms during exercise, daily, and DALDA responses were similar for each diet (p>0.11). There were no significant differences in IFABP (p=0.69) or cytokine (P>0.13) responses. A short-term GFD had no overall effect on performance, GI symptoms, well-being, and a select indicator of intestinal injury or inflammatory markers in non-celiac endurance athletes.
Article
The immune response causing celiac disease (CD) depends on the activation of intestinal CD4+ T cells by gluten-derived peptides presented by HLA-DQ2 or HLA-DQ8 molecules, the main genetic risk factor. However, additional factors are necessary to impair immune tolerance to dietary gluten, to stimulate intraepithelial lymphocytes (IEL) and to induce intestinal damage. Key Messages: Current data point to a central role of interleukin-15 (IL-15). In situ and ex vivo studies indicate that IL-15 stimulates the accumulation and cytotoxic activation of CD8+ T IEL in active CD, and that of the malignant innate-like IEL in type II refractory CD (RCDII). Other studies show that IL-15 impairs the immunoregulatory control of effector T cells, notably CD8+. Recently, animal models have been designed to investigate the respective role of CD4+ T cells and IL-15 in CD. We discuss more particularly our results in such a model, which shows that IL-15 produced in excess in the intestine can cooperate with CD4+ T cells specific for a dietary antigen to trigger a celiac-like enteropathy. In this mouse model, CD4+ T cells activated by dietary ovalbumin secreted IL-2 which, along with IL-15, stimulated the expansion of noncognate intestinal cytotoxic CD8+ T cells containing large amounts of granzyme B. In the presence of IL-15, the latter cells did not respond to regulatory T cells, and accumulated in the intestine close to epithelial damage. On the basis of these data, we propose that, in CD, gluten-specific CD4+ T cells synthesize cytokines that synergize with IL-15 to license the expansion and activation of cytotoxic IEL, which drive tissue damage. We suggest that IL-15 is a meaningful therapeutic target, notably in patients with RCDII in which malignant IEL can respond to IL-15 independently of signals provided by CD4+ T cells. © 2015 S. Karger AG, Basel.
Article
Celiac disease is a multifactorial and polygenic disease with autoimmune features. The disease is caused by an inappropriate immune response to gluten. Elimination of gluten from the diet leads to disease remission, which is the basis for today's treatment of the disease. There is an unmet need for new alternative treatments. Key Messages: Genetic findings point to adaptive immunity playing a key role in the pathogenesis of celiac disease. MHC is by far the single most important genetic factor in the disease. In addition, a number of non-MHC genes, the majority of which have functions related to T cells and B cells, also contribute to the genetic predisposition, but each of them has modest effect. The primary MHC association is with HLA-DQ2 and HLA-DQ8. These HLA molecules present gluten epitopes to CD4+ T cells which can be considered to be the master regulators of the immune reactions that lead to the disease. The epitopes which the T cells recognize are usually deamidated, and this deamidation is mediated by the enzyme transglutaminase 2 (TG2). Celiac disease patients have disease-specific antibodies. In addition to antibodies to gluten, these include autoantibodies to TG2. Antibodies to deamidated gluten are nearly as specific for celiac disease as the anti-TG2 antibodies. Both types of antibodies appear only to be produced in subjects who are HLA-DQ2 or HLA-DQ8 when they are consuming gluten. It is hardly coincidental that TG2 is implicated in T-cell epitope formation and at the same time a target for autoantibodies. Understanding this connection is one of the major challenges for obtaining a complete understanding of how gluten causes tissue destruction and remodeling of the mucosa in the small bowel. © 2015 S. Karger AG, Basel.
Article
While it is well documented and widely appreciated that ingestion of wheat (and less so rye and barley) is associated with gastrointestinal symptoms such as bloating or abdominal pain, the component of wheat to which such an effect is attributed is less well established. Key Messages: Wheat is a complex of proteins (80% gluten, 20% metabolic proteins), carbohydrates (starch, non-starch polysaccharides, fructans), lipids and other components. The majority of attention has focused on gluten as the culprit in triggering symptoms, but re-challenge studies have nearly all used wheat flour-related products (such as bread) as the stimulus. When carbohydrate-deplete gluten was used as the challenge agent, gluten-specific feelings of depression and not gut symptoms were observed in those who fulfilled strict criteria of 'non-coeliac gluten sensitivity', thereby underlining the complexity of cereals and of undertaking research in this area. Candidate components other than gluten include poorly absorbed oligosaccharides (mainly fructans), non-gluten wheat proteins such as amylase-trypsin inhibitors or wheat germ agglutinin, and exorphins released during the digestion of gluten. Specific biological and/or clinical effects associated with gluten-free diets or wheat ingestion need to be carefully dissected before attribution to gluten can be claimed. Currently, coeliac disease is the only common condition that has been unequivocally linked to gluten. Inaccurate attribution will be associated with suboptimal therapeutic advice and at least partly underlies the current gluten-free epidemic gripping the Western world. © 2015 S. Karger AG, Basel.
Article
Background Noncoeliac gluten sensitivity (NCGS) is a controversial emerging disorder. Despite reported symptoms related to the ingestion of gluten, NCGS remains a diagnosis based on the exclusion of coeliac disease, given the absence of reliable biomarkers.AimTo evaluate the prevalence, diagnostic exclusion of coeliac disease and the efficacy of a gluten-free diet (GFD) for NCGS patients.MethodsA PubMed search was performed up to December 2014. According to consensus diagnostic criteria, NCGS was defined as self-reported gluten intolerance, negative coeliac serology and absence of villous atrophy. Studies evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS) were also included.ResultsPrevalence rates of NCGS (0.5–13%) differed widely. Seventeen studies, including 1561 patients (26 children), met the inclusion criteria for NCGS. HLA haplotypes could not be linked to histology [normal or lymphocytic enteritis (LE)] in 1123 NCGS patients. HLADQ2/DQ8 haplotypes were present in 44% of NCGS patients. After advanced diagnostic techniques in 189 NCGS patients combining LE and HLADQ2/DQ8 haplotypes, 39 (20%) were reclassified as coeliac disease. There was a higher than expected family history of coeliac disease and autoimmune disorders in NCGS patients. A GFD resulted in variable results for variable, but significantly improved stool frequency in HLADQ2 positive diarrhoea-predominant IBS patients.Conclusions Prevalence rates for NCGS are extremely variable. A subset of NCGS patients might belong in the so-called ‘coeliac-lite’ disease. The benefit of a GFD for NCGS patients is currently controversial. HLADQ2 positive diarrhoea-type IBS patients might gain symptom improvement from a GFD.
Article
There is debate over the existence of nonceliac gluten sensitivity (NCGS) -intestinal and extra-intestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. We enrolled 61 adults without celiac disease or wheat allergy who believe ingestion of gluten-containing food to be the cause of their intestinal and extra-intestinal symptoms. Participants were randomly assigned to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastro-soluble capsules. After a 1 week of gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extra-intestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P=.034). Abdominal bloating (P=.040) and pain (P=.047), among the intestinal symptoms, and foggy mind (P=.019), depression (P=.020), and aphthous stomatitis (P=.025), among the extra-intestinal symptoms, were significantly more severe when subjects received gluten than placebo. In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Article
Background & aims: We investigated suspected food intolerances in patients with irritable bowel syndrome (IBS) using confocal laser endomicroscopy (CLE) for real-time visualization of structural/functional changes in the intestinal mucosa after food challenge. Patients with functional changes after food challenge (CLE+) were placed on personalized exclusion diets and followed up for long-term symptom relief. Methods: Thirty-six IBS patients with suspected food intolerance and 10 patients with Barrett's esophagus (controls) without IBS symptoms were examined by CLE at University Hospital Schleswig-Holstein (Kiel, Germany). Diluted food antigens were administered directly to the duodenal mucosa through the working channel of the endoscope. Epithelial breaks, intervillous spaces, and the number of intraepithelial lymphocytes (IEL) were measured before and after the food challenge. CLE+ patients were placed on exclusion diets, given symptom score questionnaires, and followed up for 1 year; controls resumed their previous diet. Results: CLE showed a real-time response to food antigens in 22 of 36 patients; no responses were observed in 14 of 36 patients (CLE-) or any of the controls. Baseline IELs were significantly higher in CLE+ than CLE- subjects (P = .004); numbers increased significantly after food challenge (P = .0008). Within 5 minutes of exposure of CLE+ patients to food antigens, IELs increased, epithelial leaks/gaps formed, and intervillous spaces widened. Epithelial leaks and intervillous spaces also increased significantly in CLE+ vs baseline (both P < .001). The concordance of IELs measured by CLE and conventional histology was 70.6%; they did not correlate (P = .89; r(2) = 0.027). Symptom scores improved more than 50% in CLE+ patients after a 4-week exclusion diet and increased to 74% at 12 months; symptoms continued in CLE- patients. Conclusions: Based on CLE analysis of IBS patients with a suspected food intolerance, exposure to candidate food antigens caused immediate breaks, increased intervillous spaces, and increased IELs in the intestinal mucosa. These changes are associated with patient responses to exclusion diets. Registered at clinicaltrials.gov (registration number: NCT01692613).
Article
Background: Maintaining a gluten-free diet (GFD) without an underlying diagnosis of celiac disease has enjoyed widespread acceptance in the Unites States. Methods: We performed a cross-sectional study using a GFD questionnaire in 1647 patients with inflammatory bowel diseases (IBD) participating in the CCFA Partners longitudinal Internet-based cohort. Results: A diagnosis of celiac disease and non-celiac gluten sensitivity were reported by 10 (0.6%) and 81 (4.9%) respondents, respectively. Three hundred fourteen (19.1%) participants reported having previously tried a GFD and 135 (8.2%) reported current use of GFD. Overall 65.6% of all patients, who attempted a GFD, described an improvement of their gastrointestinal symptoms and 38.3% reported fewer or less severe IBD flares. In patients currently attempting a GFD, excellent adherence was associated with significant improvement of fatigue (P < 0.03). Conclusions: In this large group of patients with IBD, a substantial number had attempted a GFD, of whom the majority had some form of improvement in gastrointestinal symptoms. Testing a GFD in clinical practice in patients with significant intestinal symptoms, which are not solely explained by the degree of intestinal inflammation, has the potential to be a safe and highly efficient therapeutic approach. Further prospective studies into mechanisms of gluten sensitivity in IBD are warranted.
Article
Reports suggest that gluten sensitivity (GS) exists in the absence of coeliac disease (CD). This clinical entity has been termed noncoeliac gluten sensitivity (NCGS). To determine the population prevalence of self-reported GS and referral characteristics to secondary care. A UK population-based questionnaire screened for GS and related symptoms. Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive coeliac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1-3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD. Clinical comparisons were made between NCGS and CD. A total of 1002 adults in the population (female 55%, mean age 39 years). The self-reported prevalence for GS was 13% (female 79%, mean age 39.5 years, P<0.0001), with 3.7% consuming a gluten-free diet and 0.8% known to have a doctor diagnosis of CD. Individuals with GS had an increased prevalence of fulfilling the Rome III criteria for irritable bowel syndrome, in comparison with those without GS (20 vs. 3.89%, odds ratio 6.23, P<0.0001).In secondary care 200 GS patients (female 84%, mean age 39.6 years) were investigated, in whom 7% were found to have CD and 93% to have NCGS. All CD patients were human leucocyte antigen DQ2 or DQ8 positive compared with 53% of NCGS cases (P=0.0003). Nutritional deficiencies (P≤0.003), autoimmune disorders (23.1 vs. 9.7%, P=0.0001) and a lower mean BMI (23.7 vs. 25.8, P=0.001) were significantly associated with CD compared with NCGS. GS is commonly self-reported with symptoms suggesting an association with irritable bowel syndrome. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD.