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

作者：Mall John-Peter Ganda; Casado-Bedmar Maite; Winberg Martin E.; Brummer Robert J.; Schoultz Ida; Keita Asa V.^*

来源：Inflammatory Bowel Diseases, 2018, 24(1): 166-178.

DOI：10.1093/ibd/izx002

• beta-glucan
• Crohn's disease
• intestinal permeability

Background: Administration of beta-glucan has shown immune-enhancing effects. Our aim was to investigate whether beta-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 beta-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 beta-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of beta-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1-and FAE-cultures were used to investigate beta-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.
Results: beta-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 beta-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of beta-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-beta-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-alpha but not IL-6 by beta-glucan. Immunofluorescence revealed more beta-glucan-uptake and higher percentage of macrophages and dendritic cells close to beta-glucan in VE of CD compared to controls.
Conclusions: We demonstrated beneficial effects of beta-glucan on intestinal barrier function and increased beta-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of beta-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.

• 出版日期2018-1