A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects

• Published in: Inflammatory bowel diseases Vol. 24; no. 1; pp. 166 - 178
• Main Authors: Ganda Mall, John-Peter, Casado-Bedmar, Maite, Winberg, Martin E, Brummer, Robert J, Schoultz, Ida, Keita, Åsa V
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-01-2018
• Subjects: Adult; beta-Glucans - administration & dosage; Case-Control Studies; Cell Membrane Permeability - drug effects; Crohn Disease - immunology; Crohn Disease - metabolism; Crohn Disease - prevention & control; Crohn’s disease; Cytokines - metabolism; Dietary Fiber - administration & dosage; Epithelium - drug effects; Epithelium - immunology; Epithelium - metabolism; Female; Humans; Ileum - drug effects; Ileum - immunology; Ileum - metabolism; intestinal permeability; Male; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Middle Aged; Mucous Membrane - drug effects; Mucous Membrane - immunology; Mucous Membrane - metabolism; Original s-Basic Science; Young Adult; β-glucan; β-glucan; intestinal permeability; Crohn's disease; Crohn’s disease
• ISSN: 1078-0998; 1536-4844; 1536-4844
• DOI: 10.1093/ibd/izx002

Abstract
Background
Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.
Methods
Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.
Results
β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.
Conclusions
We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.