Gluten-free Diet Group Research Articles

Assessment of salivary microbiota profile as a potential diagnostic tool for pediatric celiac disease

The association between oral dysbiosis and celiac disease (CD) remains poorly understood, as does the impact of CD-associated dysbiosis on disease development or exacerbation. This study aims to investigate alterations in salivary microbial composition among children with CD. In this cross-sectional study, saliva samples from 12 children with active CD (A-CD group), 14 children with CD on a gluten-free diet (GFD), and 10 healthy control (HC) children were analyzed using DNA sequencing targeting the 16S ribosomal RNA. Both patients in A-CD and GFD groups showed a significant increase (p = 0.0001) in the Bacteroidetes phylum, while the Actinobacteria phylum showed a significant decrease (p = 0.0001). Notably, the Rothia genus and R.aeria also demonstrated a significant decrease (p = 0.0001) within the both CD groups as compare to HC. Additionally, the control group displayed a significant increase (p = 0.006) in R.mucilaginosa species compared to both CD patient groups. Distinct bacterial strains were abundant in the saliva of patients with active CD, indicating a unique composition of the salivary microbiome in individuals with CD. These findings suggest that our approach to assessing salivary microbiota changes may contribute to developing noninvasive methods for diagnosing and treating CD.

Transcriptomic analysis of intestine following administration of a transglutaminase 2 inhibitor to prevent gluten-induced intestinal damage in celiac disease

Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

Effectiveness of a gluten-free diet on the autoantibody frequency of endocrine and neuron disorders in patients with celiac disease

Several possible associations between different types of autoimmune diseases have been reported, therefore this study aimed to investigate the relationship between celiac disease (CD) and some related autoimmune diseases by determining the effect of gluten on severity of these diseases. Two hundred blood samples were collected, 50 samples were withdrawn from healthy donors as a control group, 75 were collected from newly diagnosed (ND) CD patients, while the remaining blood samples (75) were obtained from the same patients after 4 months of gluten free diet (GFD) regime. Sera were separated to measure the level of anti-tissue transglutaminase IgA (tTG-IgA), anti-pituitary IgG, anti- thyroid peroxidase IgG (TPO- IgG), anti-islet IgG and anti-ganglioside IgG (IU/ml) by enzyme linked immunosorbent assay (ELISA). To analyze the results and compare between groups, GraphPad Prism was utilized. The results recorded high significant elevation (p>0.0001) in the concentrations of all autoantibodies of both ND and GFD groups compared with their concentrations in the control group. Furthermore, after 4 months of GFD, all autoantibodies concentrations revealed highly significant decreases (p>0.0001) as compared with ND. Regarding the correlation of all studied autoantibodies with anti tTG-IgA, only anti-ganglioside IgG levels were weakly correlated in pre-GFD treatment patients, meanwhile anti-ganglioside IgG and anti-pituitary IgG were also recorded weak correlations in post- GFD of CD patients. This study concluded that GFD helps to reduce the severity of endocrine and neuron autoimmune disorders in addition to CD, which have been proved by decreasing in the level of their diagnostic autoantibodies.

Effect of Gluten-Free Diet on Aortic Elasticity in Children with Celiac Disease

Background: Celiac disease is a hereditary digestive disease in children associated with an autoimmune disorder of the small intestine. This study aimed to study aortic stiffness in children with celiac disease compared with controls and assess the effects of a gluten-free diet on aortic stiffness parameters. Methods: This case-control study was conducted on 114 children with celiac disease and 57 healthy volunteers. Children with celiac disease comprised three groups: Gluten-free diet (GFD)-responsive, GFD-nonresponsive, and newly diagnosed. Systolic and diastolic diameters of the ascending aorta were recorded by M-mode echocardiography. Data were analyzed using SPSS 20. Study data had free distribution and nonparametric tests were applied for the analysis. The tests were Mann-Whitney U and Kruskal-Wallis with P value < 0.05as the significance level. Results: Aortic strain (11.15 ± 7.47 vs. 13.78 ± 6.95, P = 0.002) and aortic distensibility (6.98 ± 5.03 vs. 8.33 ± 5.13, P = 0.037) were lower in celiac disease (CD) while pressure strain elastic modulus (410.60 ± 247.45 vs. 330.71 ± 216.94, P = 0.012) and aortic strain β index (1.79 ± 0.62 vs. 1.44 ± 0.51, P < 0.001) were higher. The aortic strain significantly differed between control and response to GFD (P = 0.026), control and new diagnosis (P < 0.001), response to GFD and new diagnosis (P = 0.003), and no response to GFD and new diagnosis (P < 0.001) groups. The aortic strain β index differed significantly between control and response to GFD (P ≤ 0.001), control and new diagnosis (P < 0.001), response to GFD and no response to GFD (P = 0.035), response to GFD and new diagnosis (P = 0.002), and no response to GFD and new diagnosis (P < 0.001) groups. Aortic distensibility significantly differed between control and new diagnosis (P < 0.001), response to GFD and new diagnosis (P = 0.037), and no response to GFD and new diagnosis (P = 0.021) groups. Pressure strain elastic modulus significantly differed between control and new diagnosis (P < 0.001), response to GFD and new diagnosis (P = 0.037), and no response to GFD and new diagnosis (P = 0.021) groups. Conclusions: The present study concluded that the elasticity parameters will change due to celiac disease. Gluten-free diet had no significant effect on aortic stiffing measures except the ASβ index.

Evaluation of the effect of probiotics on celiac patients

ABSTRACT
 Aims:It was aimed to evaluate the effect of yogurt consumption containing Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophilus probiotic bacteria on the celiac markers, biochemical values and clinical symptoms of celiac diseas.
 Methods:Fifty celiac patients with positive anti-tissue transglutaminase(anti-tTG) IgA values were evaluated prospectively. The patients were divided into two groups. One group was recommended only gluten-free diet(GFD),while the other group was recommended to eat 200 mL probiotic yogurt containing Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophilus daily in addition to GFD. The change in biochemical values, vitamin levels, celiac markers and clinical symptoms of both groups was examined after three months of yogurt consumption.
 Results:Anti-tTg IgA,anti-deamidated gliadin peptide antibody(anti-DGP) IgA and anti-endomysium antibody(EMA) levels of the two groups decreased significantly after three months in both groups.There was a significant decrease in EMA levels in the probiotic yogurt+GFD group(p=0.025) when compared with GFD group. Vitamin D and ferritin levels of the probiotic yogurt+GFD group increased significantly after three months(respectively p=0.004;p=0.039). Folate, vitamin D and iron levels of GFD group increased significantly(respectively p=0.002;p=0.007;p=0.007). In both groups, clinical symptoms significantly decreased after three months. There was a significant decrease in the abdominal pain symptoms in the probiotic yogurt+GFD group when compared with GFD group(p=0.012).
 Conclusion:Gluten-free diet and consumption of yogurt containing Streptococcus thermophilus, L. delbrueckii ssp. bulgaricus and Lactobacillus acidophilus were found to be statistically significant in decreasing EMA levels and abdominal pain from irritable bowel syndrome (IBS) type symptoms of celiac patients when compared with GFD only.

The Investigation of Nutritional Status, Intestinal Permeability, and Quality of Life in People with Celiac Disease.

Celiac disease is associated with impaired intestinal epithelial barrier integrity. Its consequences affect the nutritional status and quality of life of patients. This study aimed to determine nutritional status, intestinal permeability, and quality of life in people with celiac disease. It was researched whether patients who are non-compliant to gluten-free diet have higher serum zonulin levels and intestinal permeability. The study was completed with 44 celiac patients. Dietary records and a questionnaire were used to evaluate patients' compli ance to the gluten-free diet. Dietary records were analyzed by using a nutrition analysis program. Anthropometric measurements were taken. Body compositions were analyzed to assess the nutritional status of patients. Blood samples were collected and then zonulin levels and total serum proteins were measured to evaluate intestinal permeability. Celiac Disease Questionnaire was used to assess the quality of life scores. Patients were divided into 2 groups considering compliance to the gluten-free diet and it was found that 17 patients were com pliant to the gluten-free diet, and 27 patients were non-compliant to the gluten-free diet. Serum zonulin, zonulin/total protein ratio, and intestinal permeability were higher in non-compliant to the gluten-free diet group (P < .05). There was no significant difference between anthropometric measurements, Celiac Disease Questionnaire scores, daily energy, and nutrient intakes of groups (P > .05). The content of a gluten-free diet has a decisive role in the nutritional status and quality of life of celiac patients. Additionally, zonulin levels and intestinal permeability were higher in people with celiac disease who are non-compliant to gluten-free diet.

Changes in the gut bacteriome upon gluten-free diet intervention do not mediate beta cell preservation.

We previously detected indications that beta cell function is protected by gluten-free diet (GFD) introduced shortly after the onset of childhood type 1 diabetes. The present aim was to assess whether GFD was associated with changes in the gut bacteriome composition and in its functional capacity, and whether such changes mediated the observed effects of GFD on beta cell function. Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial primarily focused on determining the role of GFD on beta cell preservation ( ClinicalTrials.gov NCT02867436). Stool samples were collected prior to the dietary intervention and then at 3-month intervals. A total of 128 samples from the GFD group and 112 from the control group were analysed for bacteriome 16S rDNA community profiles, the bacteriome functional capacity was predicted using PICRUSt2 and actual gut metabolome profiles measured using NMR. Intestinal permeability was assessed using serum zonulin concentrations at 1, 6 and 12 months and lactulose/mannitol tests at the end of intervention. Dietary questionnaires were used to ensure that the dietary intervention did not result in differences in energy or nutrient intake. The bacteriome community composition changed during the intervention with GFD: of abundant genera, a 3.3-fold decrease was noted for Bifidobacterium genus (adjusted p=1.4 × 10-4 in a DESeq2 model, p=0.026 in generalised estimating equations model), whereas a 2.4-fold increase was observed in Roseburia (adjusted p=0.02 in DESeq2 model, p=0.002 in generalised estimating equations model). The within-sample (alpha) diversity did not change, and there was no statistically significant clustering of GFD samples in the ordination graphs of beta diversity. Neither of the genera changes upon GFD intervention showed any association with the pace of beta cell loss (p>0.50), but of the remaining taxa, several genera of Bacteroidaceae family yielded suggestive signals. The faecal metabolome profile ordination correlated with that of bacteriomes but did not associate with GFD or categories of beta cell preservation. There was no indication of changes in gut permeability. The bacteriome reacted to GFD, but the changes were unrelated to the pace of beta cell capacity loss. The previously observed moderately protective effect of GFD is therefore mediated through other pathways.

Dietary Acid Load in Gluten-Free Diets: Results from a Cross-Sectional Study.

The gluten-free diet (GFD) ensures improvement of clinical symptoms in the vast majority of celiac disease (CD) patients. Despite stable CD rates in many countries, an increasing number of healthy individuals are adopting gluten-free diets, believing that this diet is an inherently healthier choice. The health effects of gluten-free diets are controversial, and a recent study added to the debate by reporting a lower acidogenic potential of this diet. The effects of the GFD on potential renal acid load (PRAL) and net endogenous acid production (NEAP)—two important markers of dietary acid load (DAL)—are poorly understood, and have never been examined in a Western population. Using cross-sectional data from the National Health and Nutrition Examination Surveys, we estimated DAL in U.S. individuals reporting a GFD and contrasted the results to the general U.S. population consuming gluten and denying special diets. The GFD was associated with significantly lower crude DAL scores, and after adjustments for confounders in multivariate regression, the results remain significant. Yet, our study could not confirm the reported alkalizing properties of the GFD. Although overall DAL scores were significantly lower in the GFD group, they were comparable to Western diets producing 50–75 mEq of acid per day.

Psychological, Physiological, and Physical Effects of Resistance Training and Personalized Diet in Celiac Women.

BackgroundGluten intolerance is a systemic process of autoimmune nature; it develops in genetically predisposed subjects with gluten ingestion. The only treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). This study was designed to evaluate adherence to a GFD, risk of an eating disorder, and nutritional status in adult CD patients undergoing different interventions.MethodsA total of 28 Spanish women, aged 40 years or more, took part in a randomized controlled trial. Each group received a different intervention: group 1, gluten-free nutrition plan + exercise (GFD + E); group 2, gluten-free nutrition plan (GFD); group 3, celiac controls (NO-GFD); and group 4, non-celiac controls (CONTROL). The training was prescribed by a sport scientist. It was based on resistance training with elastic bands; beforehand a warm-up was performed and the resistance was increased progressively. The variables studied were adherence to the GFD, risk of eating disorders, blood values, and body composition.ResultsCeliac women with personalized nutritional planning presented greater adherence to a gluten-free diet (p < 0.001). Regarding leukocytes, significant differences were observed between the GFD and control groups (p = 0.004). Perimeters and folds did not decrease significantly.ConclusionWomen with celiac disease who follow an adapted and personalized diet have a better adherence to a GFD compared to those who follow a non-professional diet, and therefore have a better immune system status (blood leukocytes).

Does a gluten-free diet lead to better glycemic control in children with type 1 diabetes? Results from a feasibility study and recommendations for future trials

BackgroundIncreasing evidence suggests a link between type 1 diabetes (T1D) and intake of gluten, but no controlled trials have examined whether a gluten-free diet (GFD) has positive effects on glycemic control in children with T1D. MethodsWe conducted a non-randomized feasibility study. Twenty-three children with newly diagnosed T1D were included and either followed a GFD (n = 14) or a normal diet (n = 9) for 12 months. Effects of diet on glycemic control were examined by measuring insulin production (c-peptide), hemoglobine A1c (HbA1c) and insulin dose adjusted A1c (IDAA1c). Degree of adherence to the GFD and effects on quality of life were also examined. ResultsChildren on a GFD showed a statistically significantly lower HbA1c at six months (P = 0.042) compared with children on a normal diet and point estimate differences indicated better glycemic control in the GFD group at 6 and 12 months. Adherence to a GFD varied but was satisfactory for a majority of children. The GFD group reported poorer quality of life at inclusion and there was a non-significant difference for quality of life between groups throughout the study. ConclusionsA strict GFD can be maintained by children with newly diagnosed T1D and may have positive effects on glycemic control. Our findings should be interpreted carefully because of small samples and possible confounding. We provide recommendations for future trials and suggest using a randomized-controlled design with 30–40 participants in each arm.

Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

The Diverse Potential of Gluten from Different Durum Wheat Varieties in Triggering Celiac Disease: A Multilevel In Vitro, Ex Vivo and In Vivo Approach.

The reasons behind the increasing prevalence of celiac disease (CD) worldwide are still not fully understood. This study adopted a multilevel approach (in vitro, ex vivo, in vivo) to assess the potential of gluten from different wheat varieties in triggering CD. Peptides triggering CD were identified and quantified in mixtures generated from simulated gastrointestinal digestion of wheat varieties (n = 82). Multivariate statistics enabled the discrimination of varieties generating low impact on CD (e.g., Saragolla) and high impact (e.g., Cappelli). Enrolled subjects (n = 46) were: 19 healthy subjects included in the control group; 27 celiac patients enrolled for the in vivo phase. Celiacs were divided into a gluten-free diet group (CD-GFD), and a GFD with Saragolla-based pasta group (CD-Sar). The diet was followed for 3 months. Data were compared between CD-Sar and CD-GFD before and after the experimental diet, demonstrating a limited ability of Saragolla to trigger immunity, although not comparable to a GFD. Ex vivo studies showed that Saragolla and Cappelli activated immune responses, although with great variability among patients. The diverse potential of durum wheat varieties in triggering CD immune response was demonstrated. Saragolla is not indicated for celiacs, yet it has a limited potential to trigger adverse immune response.

Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge

Background & AimsGluten challenge studies are instrumental in understanding the pathophysiology of celiac disease. Our aims in this study were to reveal early gluten-induced transcriptomic changes in duodenal biopsies and to find tools for clinics.MethodsDuodenal biopsies were collected from 15 celiac disease patients on a strict long-term gluten-free diet (GFD) prior to and post a gluten challenge (PGC) and from 6 healthy control individuals (DC). Biopsy RNA was subjected to genome-wide 3’ RNA-Seq. Sequencing data was used to determine the differences between the three groups and was compared to sequencing data from the public repositories. The biopsies underwent morphometric analyses.ResultsIn DC vs. GFD group comparisons, 167 differentially expressed genes were identified with 117 genes downregulated and 50 genes upregulated. In PGC vs. GFD group comparisons, 417 differentially expressed genes were identified with 195 genes downregulated and 222 genes upregulated. Celiac disease patients on a GFD were not “healthy”. In particular, genes encoding proteins for transporting small molecules were expressed less. In addition to the activation of immune response genes, a gluten challenge induced hyperactive intestinal wnt-signaling and consequent immature crypt gene expression resulting in less differentiated epithelium. Biopsy gene expression in response to a gluten challenge correlated with the extent of the histological damage. Regression models using only four gene transcripts described 97.2% of the mucosal morphology and 98.0% of the inflammatory changes observed.ConclusionsOur gluten challenge trial design provided an opportunity to study the transition from health to disease. The results show that even on a strict GFD, despite being deemed healthy, patients reveal patterns of ongoing disease. Here, a transcriptomic regression model estimating the extent of gluten-induced duodenal mucosal injury is presented.

Effect of Gluten-FREE Diet on Metabolic Control and Anthropometric Parameters in Type 1 Diabetes with Subclinical Celiac Disease: A Randomized Controlled Trial

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis. Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups. Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion. Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD. Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A.

Child and Parent Mental Health Problems in Pediatric Celiac Disease: A Prospective Study.

The aim of our study was to estimate the levels of mental health problems in children with celiac disease (CD) along with their parents' mental health status, to compare these levels with those of healthy controls and to investigate how these problems are affected by a gluten-free diet (GFD). Our study constituted 50 patients with CD at diagnosis before the initiation of a GFD (age 8.6 ± 3.7 years, group A), 39 patients with CD on a GFD for at least 12 months (age 10.4 ± 3.4 years, group B) and 38 healthy controls (age 7.7 ± 3.8 years, group C), as well as their parents. One of the parents of each child completed the Child Behaviour Checklist (CBCL) and the Symptom Checklist 90 (SCL-90-R) to evaluate the children's and parents' mental health problems, respectively. Twenty patients in group A were reevaluated at least 12 months after initiation of a GFD (group D). At diagnosis, CD patients had higher scores in the CBCL for internalizing problems than healthy controls (55.7 ± 10.3 vs 47.9 ± 15.4, P = 0.007) and their parents demonstrated increased severity of mental health problems, including anxiety and depression, than the parents of healthy controls (0.72 ± 0.49 vs 0.54 ± 0.58, P = 0.013). CD patients at diagnosis and their parents, had more mental health problems, including anxiety and depression, than healthy controls.

Gluten-Free Diet in Children with Autism Spectrum Disorders: A Randomized, Controlled, Single-Blinded Trial.

To determine whether a gluten-free diet (GFD) compared with a gluten-containing diet (GD) influences functioning of children with autism spectrum disorders (ASD), we performed a randomized, controlled, single-blinded trial. Sixty-six children (36-69months) with ASD, within the normal IQ (> 70) range, who had been on a GFD for at least 8weeks before enrollment were eligible for inclusion. After an 8-week run-in period on a GFD, the GFD group continued this diet and the GD group consumed at least one normal meal containing gluten per day for 6months. There were no differences between groups in autistic symptoms, maladaptive behaviors, or intellectual abilities after the intervention. A GFD compared with a GD did not affect functioning of children with ASD.Trial registration ClinicalTrials.gov, number NCT02280746.

1378-P: Gluten-Free Diet in Children with Recent-Onset Type 1 Diabetes without Coeliac Disease: A 12-Month Intervention Trial

Objectives: Data on the role of gluten in type 1 diabetes (T1D) are scarce. We aimed to test whether gluten-free diet (GFD) can decelerate the decline in beta-cell capacity in newly diagnosed non-celiac T1D children. Methods: Forty-six children (aged 10.2±3.3 years) were recruited into this non-randomized self-selected intervention trial: 26 started with GFD whereas 20 remained on standard diet. Main outcomes were the decline in C-peptide area under the curve (AUC) in mixed-meal tolerance tests and the differences in insulin dose, insulin dose adjusted A1c (IDAA1c) and HbA1c at 12 months. Data were analyzed as intention-to-treat by linear regression models adjusted for baseline parameters. The adherence to GFD was tested by immunoreactive gluten in stool. Results: Mean decrease in C-peptide AUC was 293 vs.484 pmol/L (p=0.3) at 6 months, and 567 vs. 919 pmol/L (p=0.1) at 12 months in GFD and control group, respectively. The GFD group had a lower insulin dose by 0.22 U/kg/day (p=0.007), lower IDAA1c by 1.5 (p=0.003) and lower mean HbA1c by 7.5 mmol/mol (p=0.01) at 12 months (Figure 1). There was no difference in daily carbohydrate intake between the groups (p=0.4). Immunoreactive gluten was found in the stool of only 3 patients. Conclusions: GFD kept over the first year after T1D diagnosis was associated with lower insulin demand and lower HbA1c, although the groups did not differ in the C-peptide dynamics. Disclosure V. Neuman: None. S. Pruhova: None. M. Kulich: None. S. Koloušková: None. J. Vosahlo: None. M. Romanova: None. L. Petruzelkova: None. B. Obermannova: None. O. Cinek: None. Z. Sumnik: None. Funding Ministry of Health of the Czech Republic (16-27994A)

Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage.

Gliadin, a component of wheat gluten known to be an important factor in the etiology of celiac disease, is related to several other diseases through its enhancing effect on intestinal paracellular permeability. We investigated the significance of gliadin in non-steroidal anti-inflammatory drug (NSAID)-induced small-intestinal damage in mice. 7-week-old C57BL/6 male mice were divided into the following groups: standard diet group, in which mice were fed with wheat-containing standard rodent diet (CE-2); gluten-free diet group, in which mice were fed with gluten-free diet (AIN-76A); and gliadin-administered group, in which mice fed with gluten-free diet were administered with gliadin (~250 mg/kg BW). Each group was subdivided into negative, healthy control group and NSAID-treated group. To some mice fed with gluten-free diet and administered with gliadin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was administered for clarification of the significance of EGFR in NSAID-induced small intestinal damage and intestinal permeability. In mice fed with a gluten-free diet, indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheat-containing standard diet. Gliadin exacerbated the NSAID-induced small-intestinal damage in mice fed with a gluten-free diet. With the administration of indomethacin, MPO activity, a marker of neutrophil infiltration into the mucosa and mRNA expression level of tumor necrosis factor α and interleukin-1β in the small intestine were higher in the gliadin-administered mice. Gliadin increased the intestinal paracellular permeability without indomethacin administration (4.3-fold) and further increased the permeability after indomethacin administration (2.1-fold). Gliadin induced phosphorylation of epidermal growth factor receptor (EGFR) in small-intestinal tissues, and erlotinib (an EGFR tyrosine kinase inhibitor) attenuated the indomethacin-induced intestinal damage and permeability exacerbated by gliadin, accompanied by inhibition of EGFR phosphorylation. These results suggest that gliadin plays an important role in the induction and exacerbation of NSAID-induced small-intestinal damage, and that increase in intestinal permeability via the EGFR signalling pathway is involved in its mechanism.

Comparison between gluten-free regime and regime with gluten in symptoms of patients with irritable bowel syndrome (IBS)

Background and Objective:Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder and accounts for most of the referrals of patients to gastroenterologists. Given the high prevalence of this syndrome and its significant effect on the reduced quality of life of patients, the present study aimed to investigate the effect of using gluten-containing or gluten-free diet on symptoms of patients with irritable bowel syndrome.Materials and Methods:In this trial, 140 patients with irritable bowel syndrome who referred to Imam Khomeini Hospital (2006) were randomly divided into two groups based on Rome III criteria. Seventy patients received a gluten-free diet and rest patent received a regular diet as control group for 12 weeks. In order to compare the quantitative characteristics, independent samples T-test was used, while Mann-Whitney and Z-tests were used to compare the qualitative characteristics.Findings:There was no significant difference between the control group (9.8 ± 37 years) and the group with gluten-free diet (0.2 ± 37 years) in terms of mean age. The effect of gluten-free diet on intestinal gas, fecal consistency, urgent need for expulsion, and insufficient defecation were higher than in control group. Although abdominal pain and reduced frequency of bowel movements were higher in the control group than gluten-free diet group (P < 0.05). The positive response to general improvement in the gluten-free group and in the control group was 67% and 52%, respectively.Conclusion:According to present results, providing gluten-free diet could be improved patient treatment's symptoms. Also, it seemed that the duration of treatment can lead to better therapeutic outcomes.

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study.

The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. Analytical cross-sectional study in a tertiary-level center. Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.