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A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
Örebro universitet, Institutionen för medicinska vetenskaper. (Nutrition-Gut-Brain Interactions Research Centre)
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Örebro universitet, Institutionen för medicinska vetenskaper. (Nutrition-Gut-Brain Interactions Research Centre)ORCID-id: 0000-0002-0362-0008
Visa övriga samt affilieringar
2017 (Engelska)Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, nr 1, s. 166-178Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Lippincott-Raven Publishers , 2017. Vol. 24, nr 1, s. 166-178
Nyckelord [en]
Crohn’s disease, intestinal permeability, β-glucan
Nationell ämneskategori
Gastroenterologi
Identifikatorer
URN: urn:nbn:se:oru:diva-63994DOI: 10.1093/ibd/izx002ISI: 000427524400018PubMedID: 29272475OAI: oai:DiVA.org:oru-63994DiVA, id: diva2:1172326
Forskningsfinansiär
Stiftelsen för strategisk forskning (SSF), RB13-016Vetenskapsrådet, 2014-02537
Anmärkning

Funding Agency:

LIONS research foundation

Tillgänglig från: 2018-01-09 Skapad: 2018-01-09 Senast uppdaterad: 2018-08-13Bibliografiskt granskad
Ingår i avhandling
1. Non-digestible Polysaccharides and Intestinal Barrier Function: specific focus on its efficacy in elderly and patients with Crohn’s disease
Öppna denna publikation i ny flik eller fönster >>Non-digestible Polysaccharides and Intestinal Barrier Function: specific focus on its efficacy in elderly and patients with Crohn’s disease
2018 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

A large number of elderly suffer from gastrointestinal (GI) symptoms such as constipation and diarrhoea. The underlying mechanisms of age-acquired GI symptoms are not well studied but are necessary to clarify in order to recommend the right treatment. Non-digestible polysaccharides (NPS) are dietary fibres that could have beneficial effects on the intestinal immune system and barrier function, although their efficacy needs to be evaluated. Paper I showed that elderly with GI symptoms have significantly higher small intestinal permeability than a general elderly population, along with a stronger association to psychological distress. In Paper II we performed a randomised controlled trial with a general population of elderly that consumed either placebo, the NPS’s arabinoxylan or oat β-glucan for a period of 6 weeks. No protective effects were observed related to indomethacin-induced intestinal hyperpermeability, inflammatory markers, or self-reported health if compared to placebo. Paper III showed that stimulation with a yeast-derived β-glucan significantly attenuated Compound (C) 48/80-induced hyperpermeability in colonic biopsies from elderly with GI symptoms mounted in Ussing chambers, but not in young healthy adults. Arabinoxylan attenuated only C48/80-induced transcellular permeability in elderly but both paracellular and transcellular permeability in young healthy adults. Paper IV showed that the same yeast-derived β-glucan from paper III could cross the epithelium of ileal tissues from patients with Crohn’s disease (CD) and non-CD controls, mounted in Ussing chambers, and attenuate C48/80-induced hyperpermeability. In conclusion, we found that elderly with GI symptoms display a deteriorated barrier function and that administration of selective NPS can have beneficial effect on intestinal permeability in selective populations.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro University, 2018. s. 121
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 180
Nyckelord
Non-digestible polysachharides, beta-glucan, arabinoxylan, barrier function, permeability, Ussing chamber, elderly, Crohn’s disease
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
urn:nbn:se:oru:diva-66055 (URN)978-91-7529-246-5 (ISBN)
Disputation
2018-06-08, Örebro universitet, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2018-03-26 Skapad: 2018-03-26 Senast uppdaterad: 2018-05-08Bibliografiskt granskad

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Ganda Mall, John-PeterBrummer, Robert JanSchoultz, Ida

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