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  • 1.
    Ganda Mall, John Peter
    et al.
    Örebro University, School of Medical Sciences.
    Löfvendahl, Lisa
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Keita, Å. V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 13404Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (β)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. β-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.

  • 2.
    Ganda Mall, John-Peter
    Örebro University, School of Medical Sciences.
    Non-digestible Polysaccharides and Intestinal Barrier Function: specific focus on its efficacy in elderly and patients with Crohn’s disease2018Doctoral thesis, comprehensive summary (Other academic)
    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.

    List of papers
    1. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
    Open this publication in new window or tab >>Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
    Show others...
    2018 (English)In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, no 1, article id 75Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    BioMed Central, 2018
    Keywords
    Older adults; Gastrointestinal symptoms; Intestinal barrier function; Psychological distress
    National Category
    Geriatrics
    Identifiers
    urn:nbn:se:oru:diva-66053 (URN)10.1186/s12877-018-0767-6 (DOI)000428260300001 ()29554871 (PubMedID)2-s2.0-85044174344 (Scopus ID)
    Funder
    Knowledge Foundation, 20110225
    Note

    Funding Agencies:

    Bo Rydins stiftelse  F0514 

    Faculty of Medicine and Health at Örebro University  

    Diarrheal Disease Research Centre, Linköping University  

    Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2019-12-20Bibliographically approved
    2. Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
    Open this publication in new window or tab >>Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-66863 (URN)
    Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2019-12-20Bibliographically approved
    3. Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
    Open this publication in new window or tab >>Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-66866 (URN)
    Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2018-05-04Bibliographically approved
    4. A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
    Open this publication in new window or tab >>A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
    Show others...
    2017 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed) 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.

    Place, publisher, year, edition, pages
    Lippincott-Raven Publishers, 2017
    Keywords
    Crohn’s disease, intestinal permeability, β-glucan
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-63994 (URN)10.1093/ibd/izx002 (DOI)000427524400018 ()29272475 (PubMedID)
    Funder
    Swedish Foundation for Strategic Research , RB13-016Swedish Research Council, 2014-02537
    Note

    Funding Agency:

    LIONS research foundation

    Available from: 2018-01-09 Created: 2018-01-09 Last updated: 2018-08-13Bibliographically approved
  • 3.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Casado-Bedmar, Maite
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winberg, Martin E.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed)
    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.

  • 4.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Fart, Frida
    Örebro University, School of Medical Sciences.
    Sabet, Julia
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl-Mårten
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert J.
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trialManuscript (preprint) (Other academic)
  • 5.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Löfvendahl, Lisa
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptomsManuscript (preprint) (Other academic)
  • 6.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Östlund-Lagerström, Lina
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Nutrition and Physical Activity Research Centre, Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Algilani, Samal
    Örebro University, School of Health Sciences.
    Rasoal, Dara
    Örebro University, School of Health Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    V. Keita, Åsa
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?2018In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, no 1, article id 75Article in journal (Refereed)
    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.

  • 7.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ganda-Mall, John-Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Edebol-Carlman, Hanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    The Role of the Gut Microbiota in Brain Function2015In: Probiotics and Prebiotics: Current Research and Future Trends / [ed] Koen Venema & Ana Paula do Carmo, Poole, UK: Caister Academic Press, 2015Chapter in book (Refereed)
  • 8.
    Rangel, Ignacio
    et al.
    Örebro University, School of Medical Sciences.
    Ganda Mall, John Peter
    Örebro University, School of Medical Sciences.
    Roger, Willén
    Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden.
    Sjöberg, Fei
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of Gαi2-deficient mice2016In: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 92, no 7, article id fiw098Article in journal (Refereed)
    Abstract [en]

    An altered immune response and gut microbiota have been associated with the pathology of Inflammatory Bowel Diseases (IBD). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (Gαi2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus High gene expression levels of IL-17 and IFN-γ in colon and caecum were detected in Gαi2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-γ and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.

  • 9.
    Rangel, Ignacio
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ganda-Mall, John-Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sjöberg, F.
    University of Gothenburg, Gothenburg, Sweden.
    Willen, R.
    Univ Uppsala Hosp, Uppsala, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Alterations in gut microbiota composition in tissues and feces of G alpha i2(-/-) mice with colitis in parallel with enhanced cytokine secretion2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 168-169Article in journal (Other academic)
  • 10.
    Östlund-Lagerström, Lina
    et al.
    Örebro University, School of Medical Sciences.
    Ganda Mall, John-Peter
    Örebro University, School of Medical Sciences.
    Algilani, Samal
    Örebro University, School of Health Sciences.
    Rasoal, Dara
    Örebro University, School of Health Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Low levels of inflammation and oxidative stress in senior orienteering athletesManuscript (preprint) (Other academic)
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