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Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet-Results of a Randomized, Placebo-Controlled, Pilot Trial.

ABSTRACT: Abnormalities in the intestinal barrier are a possible cause of celiac disease (CD) development. In animal studies, the positive effect of prebiotics on the improvement of gut barrier parameters has been observed, but the results of human studies to date remain inconsistent. Therefore, this study aimed to evaluate the effect of twelve-week supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (10 g per day) on the intestinal permeability in children with CD treated with a GFD. A pilot, randomized, placebo-controlled nutritional intervention was conducted in 34 children with CD, being on a strict GFD. Sugar absorption test (SAT) and the concentrations of intestinal permeability markers, such as zonulin, intestinal fatty acid-binding protein, claudin-3, calprotectin, and glucagon-like peptide-2, were measured. We found that the supplementation with prebiotic did not have a substantial effect on barrier integrity. Prebiotic intake increased excretion of mannitol, which may suggest an increase in the epithelial surface. Most children in our study seem to have normal values for intestinal permeability tests before the intervention. For individuals with elevated values, improvement in calprotectin and SAT was observed after the prebiotic intake. This preliminary study suggests that prebiotics may have an impact on the intestinal barrier, but it requires confirmation in studies with more subjects with ongoing leaky gut.

SUBMITTER: Drabinska N

PROVIDER: S-EPMC7352250 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet-Results of a Randomized, Placebo-Controlled, Pilot Trial.

Drabińska Natalia N Krupa-Kozak Urszula U Jarocka-Cyrta Elżbieta E

Nutrients 20200610 6

Abnormalities in the intestinal barrier are a possible cause of celiac disease (CD) development. In animal studies, the positive effect of prebiotics on the improvement of gut barrier parameters has been observed, but the results of human studies to date remain inconsistent. Therefore, this study aimed to evaluate the effect of twelve-week supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (10 g per day) on the intestinal permeability in children with CD tre ...[more]

PMID: 32531982

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Project description:BackgroundA lifelong gluten-free diet (GFD) is regarded as the only proven and accepted therapy for coeliac disease (CD). However, even patients who strictly follow a GFD often suffer from intestinal symptoms and malabsorption. Selective modulation of intestinal microbiota with prebiotics could remedy various symptoms associated with CD. The use of prebiotics in the treatment of intestinal diseases remains insufficiently investigated. To our knowledge, this study makes the first attempt to evaluate the effect of prebiotic supplementation on gastrointestinal symptoms and nutritional status of children with CD. We hypothesized that adherence to a GFD supplemented with oligofructose-enriched inulin (Synergy 1) would deliver health benefits to children suffering from CD without any side effects, and that it would alleviate intestinal inflammation, restore and stabilize gut microbial balance and reverse nutritional deficiencies through enhanced absorption of vitamins and minerals.MethodsA randomized, placebo-controlled clinical trial was designed to assess the impact of the Synergy 1 on paediatric CD patients following a GFD. We randomized 34 children diagnosed with CD into an intervention group receiving 10 g of the Synergy 1 supplement daily and a placebo group (receiving maltodextrin) during a 12-week nutritional intervention. Selected biochemical parameters, nutritional status and the characteristics of faecal bacteria will be determined in samples collected before and after the intervention. Analysis of vitamins and amino acids concentration in biological fluids will allow to assess the dietary intake of crucial nutrients. The compliance to a GFD will be confirmed by a Food Frequency Questionnaire (FFQ-6) and the analysis of serum anti-tissue transglutaminase and faecal gluten immunogenic peptides (GIP).ConclusionThe identification of the beneficial effects of the Synergy 1 supplement on children with CD could have important implications for nutritional recommendations for CD patients and for alleviating the harmful effects of the disease.Trial registrationClinicalTrials.gov Registration Number: NCT03064997 .

Project description:Background & Aims: Traditional celiac disease diagnostics based on histomorphometric evaluations are liable to misinterpretations due to the common technical flaws e.g. wrong orientation of the biopsy and subjective errors are relatively common e.g. interobserver errors. We envisioned that there is a need for molecular histomorphometric tool that obviates these error sources yielding an objective ratio instead. Gene expression determine the state of a tissue, so the changes in expression may be associated with the severity of lesions during CD and can be used to classify it. Methods: 15 CD patients, who have been at least one year on gluten-free diet, were enrolled. All participants were biopsied before and after the gluten challenge (10 weeks, 4 grams of gluten daily). 6 healthy non-CD individuals were included as controls. Biopsies were taken on PAXgene biological fixative and embedded in paraffin and Vh/Cd ratio was assessed. RNA was extracted from the same sections and subjected to genome-wide 3’RNA-sequencing. Sequencing data was used to determine differentially expressed genes and regression model, that successfully describes the mucosal damage, was created and tested in independent material. Results: 167 differentially expressed genes were identified in healthy vs. treated CD comparisons with 117 genes downregulated and 50 genes upregulated. 415 differentially expressed genes were identified in Post gluten challenge to Treated CD comparisons with 195 genes downregulated and 220 genes upregulated. 119 genes whose expression highly correlates to Vh/Cd ratio (Spearman’s rank correlation coefficient, |rho|>0.7) were identified. Gene ontology analyses show that genes involved in cellular response to cytokines, including interferons, were over-represented. Stepwise regression allowed us computationally cut down the number of genes, that describe Vh/Cd ratio changes, to 7 and IELs number to 5. Created models describe 98.9% of observed Vh/Cd and 97.5% of IELs number variabilities; there is a strong correlation between the model’s predicted and observed ratios. Conclusions: Adoption of molecular histomorphometry, with our selected set of target genes, is quantitative and reliable way of estimating gluten-induced mucosal injury and inflammation. By including this technology one can overcome the typical shortcomings common in celiac disease diagnostics based on traditional histomorphometry analyses alone. Likewise, molecular histomorphometry is a promising instrument when incorporated in clinical trials where assessing drug efficacy on mucosal health is paramount. In addition, despite deemed healthy, based on traditional histomorphometric analyses, celiac patients on gluten free diet have significantly distinctive molecular histomorphometric pattern when compared to healthy controls.

Dataset Information

Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet-Results of a Randomized, Placebo-Controlled, Pilot Trial.

Publications

Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet-Results of a Randomized, Placebo-Controlled, Pilot Trial.

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