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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

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          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.

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          Leaky gut and autoimmune diseases.

          Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.
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            Strengthening of the intestinal epithelial tight junction by Bifidobacterium bifidum

            Epithelial barrier dysfunction has been implicated as one of the major contributors to the pathogenesis of inflammatory bowel disease. The increase in intestinal permeability allows the translocation of luminal antigens across the intestinal epithelium, leading to the exacerbation of colitis. Thus, therapies targeted at specifically restoring tight junction barrier function are thought to have great potential as an alternative or supplement to immunology-based therapies. In this study, we screened Bifidobacterium, Enterococcus, and Lactobacillus species for beneficial microbes to strengthen the intestinal epithelial barrier, using the human intestinal epithelial cell line (Caco-2) in an in vitro assay. Some Bifidobacterium and Lactobacillus species prevented epithelial barrier disruption induced by TNF-α, as assessed by measuring the transepithelial electrical resistance (TER). Furthermore, live Bifidobacterium species promoted wound repair in Caco-2 cell monolayers treated with TNF-α for 48 h. Time course 1H-NMR-based metabonomics of the culture supernatant revealed markedly enhanced production of acetate after 12 hours of coincubation of B. bifidum and Caco-2. An increase in TER was observed by the administration of acetate to TNF-α-treated Caco-2 monolayers. Interestingly, acetate-induced TER-enhancing effect in the coculture of B. bifidum and Caco-2 cells depends on the differentiation stage of the intestinal epithelial cells. These results suggest that Bifidobacterium species enhance intestinal epithelial barrier function via metabolites such as acetate.
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              Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin.

              Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g/day) and randomly allocated to receive either oligofructose-enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 +/- 659 microg/g; day 7: 1033 +/- 393 microg/g, P < 0.05) but not in the placebo group (day 0: 5834 +/- 1563 microg/g; day 7: 4084 +/- 1395 microg/g, n.s.). Changes in faecal concentration of human DNA were not significant. In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 June 2020
                June 2020
                : 12
                : 6
                : 1736
                Affiliations
                [1 ]Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, 10-748 Olsztyn, Poland; n.drabinska@ 123456pan.olsztyn.pl
                [2 ]Department of Pediatrics, Gastroenterology, and Nutrition, Collegium Medicum, University of Warmia & Mazury, 10-719 Olsztyn, Poland
                Author notes
                [* ]Correspondence: u.krupa-kozak@ 123456pan.olsztyn.pl (U.K.-K.); ejarocka@ 123456op.pl (E.J.-C.); Tel.: +48-89-523-46-18 (U.K.-K.); +48-89-539-33-69 (E.J.-C.)
                Author information
                https://orcid.org/0000-0001-5324-5982
                https://orcid.org/0000-0001-8580-2851
                https://orcid.org/0000-0002-0919-6615
                Article
                nutrients-12-01736
                10.3390/nu12061736
                7352250
                32531982
                0c10ad09-2339-4f7a-b164-7a1b71410652
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 May 2020
                : 09 June 2020
                Categories
                Article

                Nutrition & Dietetics
                intestinal permeability,leaky gut,gut barrier,celiac disease,prebiotic,gluten-free diet,randomized controlled trial,gluten immunogenic peptides,sugar absorption test

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