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Non-digestible Polysaccharides and Intestinal Barrier Function: specific focus on its efficacy in elderly and patients with Crohn’s disease
Örebro universitet, Institutionen för medicinska vetenskaper.ORCID-id: 0000-0002-2120-7743
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 [en]
Non-digestible polysachharides, beta-glucan, arabinoxylan, barrier function, permeability, Ussing chamber, elderly, Crohn’s disease
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
URN: urn:nbn:se:oru:diva-66055ISBN: 978-91-7529-246-5 (tryckt)OAI: oai:DiVA.org:oru-66055DiVA, id: diva2:1193037
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
Delarbeten
1. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
Öppna denna publikation i ny flik eller fönster >>Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
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2018 (Engelska)Ingår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, nr 1, artikel-id 75Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.

METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).

RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.

CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2018
Nyckelord
Older adults; Gastrointestinal symptoms; Intestinal barrier function; Psychological distress
Nationell ämneskategori
Geriatrik
Identifikatorer
urn:nbn:se:oru:diva-66053 (URN)10.1186/s12877-018-0767-6 (DOI)000428260300001 ()29554871 (PubMedID)2-s2.0-85044174344 (Scopus ID)
Forskningsfinansiär
KK-stiftelsen, 20110225
Anmärkning

Funding Agencies:

Bo Rydins stiftelse  F0514 

Faculty of Medicine and Health at Örebro University  

Diarrheal Disease Research Centre, Linköping University  

Tillgänglig från: 2018-03-27 Skapad: 2018-03-27 Senast uppdaterad: 2018-05-04Bibliografiskt granskad
2. Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
Öppna denna publikation i ny flik eller fönster >>Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
urn:nbn:se:oru:diva-66863 (URN)
Tillgänglig från: 2018-05-04 Skapad: 2018-05-04 Senast uppdaterad: 2018-05-04Bibliografiskt granskad
3. Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
Öppna denna publikation i ny flik eller fönster >>Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
urn:nbn:se:oru:diva-66866 (URN)
Tillgänglig från: 2018-05-04 Skapad: 2018-05-04 Senast uppdaterad: 2018-05-04Bibliografiskt granskad
4. A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
Öppna denna publikation i ny flik eller fönster >>A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
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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
Nyckelord
Crohn’s disease, intestinal permeability, β-glucan
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-63994 (URN)10.1093/ibd/izx002 (DOI)000427524400018 ()29272475 (PubMedID)
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: 2018-05-04Bibliografiskt granskad

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