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  • 1.
    Algilani, Samal
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Östlund-Lagerström, Lina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kihlgren, Annica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Blomberg, Karin
    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. Örebro University Hospital.
    Schoultz, Ida
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Exploring the concept of optimal functionality in old age2014In: Journal of Multidisciplinary Healthcare, ISSN 1178-2390, E-ISSN 1178-2390, Vol. 7, p. 69-79Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Aging is characterized by loss of function and represents a perspective that puts the focus on the negative aspects of aging. Thus, it is fundamental to shift the focus from loss of function to maintaining good health and personal satisfaction through life; in other words, to promote optimal functionality at a level appropriate for older adults. However, it is not yet known what constitutes optimal functionality from the older adult's own perspective.

    OBJECTIVE: To explore the concept of optimal functionality in old age from the older adult's perspective (ie, people over 65 years of age) in industrialized Western countries.

    METHODS: We undertook a scoping review and searched two electronic databases (PubMed and the Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from January 2002 to July 2013 for scientific studies, using the key search term personal satisfaction. In total, 25 scientific studies were analyzed.

    RESULTS: Only six of the included articles applied a qualitative methodology. By analyzing the results of these articles, three major themes were identified as cornerstones in the concept of optimal functionality at old age: 1) self-related factors (eg, mental well-being); 2) body-related factors (eg, physical well-being); and 3) external factors equal to demographic and environmental factors.

    CONCLUSION: There is a lack of qualitative studies in the current literature, and hence of what constitutes optimal functionality from the older adult's perspective. The results outlined in this review identify three cornerstones (self-related factors, body-related factors, and external factors) of what constitutes optimal functionality at old age. However, it is vital that these findings are taken further and are evaluated through qualitative studies to reflect older adults' opinions.

  • 2.
    Algilani, Samal
    et al.
    Örebro University, School of Health Sciences.
    Östlund-Lagerström, Lina
    Örebro University, School of Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Schröder, Agneta
    Örebro University, School of Health Sciences.
    Mental health as a prerequisite for functioning as optimally as possible in old age: a phenomenological approachManuscript (preprint) (Other academic)
  • 3.
    Algilani, Samal
    et al.
    Örebro University, School of Health Sciences.
    Östlund-Lagerström, Lina
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Brummer, Robert J.
    Örebro University, School of Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health Sciences.
    Increasing the qualitative understanding of optimal functionality in older adults: a focus group based study2016In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 16, no 1, article id 70Article in journal (Refereed)
    Abstract [en]

    Background: Decreased independence and loss of functional ability are issues regarded as inevitably connected to old age. This ageism may have negative influences on older adults' beliefs about aging, making it difficult for them to focus on their current ability to maintain a good health. It is therefore important to change focus towards promoting Optimal Functionality (OF). OF is a concept putting the older adult's perspective on health and function in focus, however, the concept is still under development. Hence, the aim was to extend the concept of optimal functionality in various groups of older adults.

    Methods: A qualitative study was conducted based on focus group discussions (FGD). In total 6 FGDs were performed, including 37 older adults from three different groups: group 1) senior athletes, group 2) free living older adults, group 3) older adults living in senior living homes. All data was transcribed verbatim and analyzed following the process of deductive content analysis.

    Results: The principal outcome of the analysis was "to function as optimally as you possibly can", which was perceived as the core of the concept. Further, the concept of OF was described as multifactorial and several new factors could be added to the original model of OF. Additionally the findings of the study support that all three cornerstones comprising OF have to occur simultaneously in order for the older adult to function as optimal as possible.

    Conclusions: OF is a multifaceted and subjective concept, which should be individually defined by the older adult. This study further makes evident that older adults as a group are heterogeneous in terms of their preferences and views on health and should thus be approached as such in the health care setting. Therefore it is important to promote an individualized approach as a base when caring for older adults.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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)
  • 7.
    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)
  • 8.
    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.

  • 9.
    Keita, A. V.
    et al.
    Linköping University, Linköping, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Ost, A.
    Aleris Medilab, Dept Pathol & Cytol, Täby, Sweden.
    Magana, C. D. L.
    Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Gut barrier dysfunction: a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S1-S1Article in journal (Other academic)
  • 10.
    Keita, Åsa V.
    et al.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences. Department of Medical Sciences.
    Öst, Åke
    Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden.
    Magana, Carlos D. L.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences. Department of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Gut barrier dysfunction: a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 10, p. 1200-1209Article in journal (Refereed)
    Abstract [en]

    Background and aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease we aimed to assess if the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function.

    Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease (monozygotic n=9, dizygotic n=6) and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to51Chromium (Cr)-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins.

    Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min both with Acetylsalicylic acid (p<0.001) and without (p<0.001) when compared to controls. A significant increase in 51Cr-EDTA flux was seen already at 20 minutes in healthy monozygotic co-twins compared to controls (p≤0.05) when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins (p<0.05) and affected twins (p<0.05) compared to external controls, while ELISA only showed lower tricellulin in Crohn's disease twins (p<0.05).

    Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation rather than representing a primary defect.

  • 11.
    Ragnarsson, Eva G. E.
    et al.
    Department of Pharmacy, Uppsala University, Uppsala.
    Schoultz, Ida
    Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Gullberg, Elisabet
    Department of Pharmacy, Uppsala University, Uppsala; Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Carlsson, Anders H.
    Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Tafazoli, Farideh
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lerm, Maria
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Magnusson, Karl-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Söderholm, Johan D.
    Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping.
    Artursson, Per
    Department of Pharmacy, Uppsala University, Uppsala.
    Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis2008In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 88, no 11, p. 1215-26Article in journal (Refereed)
    Abstract [en]

    Crohn's disease is characterized by a defect in intestinal barrier function, where bacteria are considered the most important inflammation-driving factor. Enteric bacteria, including E. coli and Yersinia spp, affect tight junctions in enterocytes, but little is known about bacterial effects on the transcellular pathway. Our objective was to study the short-term effects of Y. pseudotuberculosis on uptake of nanoparticles across human villus epithelium. Monolayers of human colon epithelium-derived Caco-2 cells and biopsies of normal human ileum were studied after 2 h exposure to Y. pseudotuberculosis expressing (inv+) or lacking (inv-) the bacterial adhesion molecule, invasin. Transepithelial transport of fluorescent nanoparticles (markers of transcytosis) was quantified by flow cytometry, and mechanisms explored by using inhibitors of endocytosis. Epithelial expressions of beta1-integrin and particle uptake pathways were studied by confocal microscopy. The paracellular pathway was assessed by electrical resistance (TER), mannitol flux, and expression of tight junction proteins occludin and caludin-4 by confocal microscopy. Inv+ Y. pseudotuberculosis adhered to the apical surface of epithelial cells and induced transcytosis of exogenous nanoparticles across Caco-2 monolayers (30-fold increase, P<0.01) and ileal mucosa (268+/-47% of control; P<0.01), whereas inv bacteria had no effect on transcytosis. The transcytosis was concentration-, particle size- and temperature-dependent, and possibly mediated via macropinocytosis. Y. pseudotuberculosis also induced apical expression of beta1-integrin on epithelial cells. A slight drop in TER was seen after exposure to inv+ Y. pseudotuberculosis, whereas mannitol flux and tight junction protein expression was unchanged. In summary, Y. pseudotuberculosis induced apical expression of beta1-integrin and stimulated uptake of nanoparticles via invasin-dependent transcytosis in human intestinal epithelium. Our findings suggest that bacterial factors may initiate transcytosis of luminal exogenous particles across human ileal mucosa, thus presenting a novel mechanism of intestinal barrier dysfunction.

  • 12.
    Rajan, Sukithar K.
    et al.
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Phylogenetic microbiota profiling in fecal samples depends on combination of sequencing depth and choice of NGS analysis method2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 9, article id e0222171Article in journal (Refereed)
    Abstract [en]

    The human gut microbiota is well established as an important factor in health and disease. Fecal sample microbiota are often analyzed as a proxy for gut microbiota, and characterized with respect to their composition profiles. Modern approaches employ whole genome shotgun next-generation sequencing as the basis for these analyses. Sequencing depth as well as choice of next-generation sequencing data analysis method constitute two main interacting methodological factors for such an approach. In this study, we used 200 million sequence read pairs from one fecal sample for comparing different taxonomy classification methods, using default and custom-made reference databases, at different sequencing depths. A mock community data set with known composition was used for validating the classification methods. Results suggest that sequencing beyond 60 million read pairs does not seem to improve classification. The phylogeny prediction pattern, when using the default databases and the consensus database, appeared to be similar for all three methods. Moreover, these methods predicted rather different species. We conclude that the choice of sequencing depth and classification method has important implications for taxonomy composition prediction. A multi-method-consensus approach for robust gut microbiota NGS analysis is recommended.

  • 13.
    Schoultz, Ida
    et al.
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Medical Faculty, Linköping University, Linköping, Sweden.
    Cellular and Molecular Therapeutic Targets in Inflammatory Bowel Disease-Focusing on Intestinal Barrier Function2019In: Cells, ISSN 2073-4409, Vol. 8, no 2, article id 193Article, review/survey (Refereed)
    Abstract [en]

    The human gut relies on several cellular and molecular mechanisms to allow for an intact and dynamical intestinal barrier. Normally, only small amounts of luminal content pass the mucosa, however, if the control is broken it can lead to enhanced passage, which might damage the mucosa, leading to pathological conditions, such as inflammatory bowel disease (IBD). It is well established that genetic, environmental, and immunological factors all contribute in the pathogenesis of IBD, and a disturbed intestinal barrier function has become a hallmark of the disease. Genetical studies support the involvement of intestinal barrier as several susceptibility genes for IBD encode proteins with key functions in gut barrier and homeostasis. IBD patients are associated with loss in bacterial diversity and shifts in the microbiota, with a possible link to local inflammation. Furthermore, alterations of immune cells and several neuro-immune signaling pathways in the lamina propria have been demonstrated. An inappropriate immune activation might lead to mucosal inflammation, with elevated secretion of pro-inflammatory cytokines that can affect the epithelium and promote a leakier barrier. This review will focus on the main cells and molecular mechanisms in IBD and how these can be targeted in order to improve intestinal barrier function and reduce inflammation.

  • 14.
    Schoultz, Ida
    et al.
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    McKay, Catherine M.
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    Graepel, Rabea
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    Phan, Van C.
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    Wang, Arthur
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    Söderholm, Johan
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    McKay, Derek M.
    Gastrointestinal Research Group, Department of Physiology and Pharmacology, The Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada.
    Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C2012In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 303, no 5, p. G536-G545Article in journal (Refereed)
    Abstract [en]

    The enteric epithelium must absorb nutrients and water and act as a barrier to the entry of luminal material into the body; this barrier function is a key component of innate immunity. Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy occurs via inhibition of prostaglandin synthesis and perturbed epithelial mitochondrial activity. Here, the direct effect of NSAIDs [indomethacin, piroxicam (cyclooxygenase 1 and 2 inhibitors), and SC-560 (a cyclooxygenase 1 inhibitor)] on the barrier function of human T84 epithelial cell line monolayers was assessed by transepithelial electrical resistance (TER) and internalization and translocation of a commensal Escherichia coli. Exposure to E. coli in the presence and absence of drugs for 16 h reduced TER; however, monolayers cotreated with E. coli and indomethacin, but not piroxicam or SC-560, displayed significant increases in internalization and translocation of the bacteria. This was accompanied by increased reactive oxygen species (ROS) production, which was also increased in epithelia treated with E. coli only. Colocalization revealed upregulation of superoxide synthesis by mitochondria in epithelia treated with E. coli + indomethacin. Addition of antioxidants (vitamin C or a green tea polyphenol, epigallocathechin gallate) quenched the ROS and prevented the increase in E. coli internalization and translocation evoked by indomethacin, but not the drop in TER. Evidence of increased apoptosis was not observed in this model. The data implicate epithelial-derived ROS in indomethacin-induced barrier dysfunction and show that a portion of the bacteria likely cross the epithelium via a transcellular pathway. We speculate that addition of antioxidants as dietary supplements to NSAID treatment regimens would reduce the magnitude of decreased barrier function, specifically the transepithelial passage of bacteria.

  • 15.
    Schoultz, Ida
    et al.
    Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute of Infection Immunity and Inflammation, University of Calgary, Calgary, Canada .
    Söderholm, Johan D.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    McKay, Derek M.
    Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute of Infection Immunity and Inflammation, University of Calgary, Calgary, Canada .
    Is metabolic stress a common denominator in inflammatory bowel disease?2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 9, p. 2008-18Article, review/survey (Refereed)
    Abstract [en]

    The enteric epithelium represents the major boundary between the outside world and the body, and in the colon it is the interface between the host and a vast and diverse microbiota. A common feature of inflammatory bowel disease (IBD) is decreased epithelial barrier function, and while a cause-and-effect relationship can be debated, prolonged loss of epithelial barrier function (whether this means the ability to sense bacteria or exclude them) would contribute to inflammation. While there are undoubtedly individual nuances in IBD, we review data in support of metabolic stress--that is, perturbed mitochondrial function--in the enterocyte as a contributing factor to the initiation of inflammation and relapses in IBD. The postulate is presented that metabolic stress, which can arise as a consequence of a variety of stimuli (e.g., infection, bacterial dysbiosis, and inflammation also), will reduce epithelial barrier function and perturb the enterocyte-commensal flora relationship and suggest that means to negate enterocytic metabolic stress should be considered as a prophylactic or adjuvant therapy in IBD.

  • 16.
    Schoultz, Ida
    et al.
    Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Verma, Deepti
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Halfvarson, Jonas
    Department of Internal Medicine, Division of Gastroenterology,örebro University Hospital ,Örebro , Sweden.
    Törkvist, Leif
    Karolinska Institutet, IBD-Unit at Karolinska University Hospital-Huddinge , Stockholm , Sweden.
    Fredrikson, Mats
    Division of Occupational and Environmental Medicine, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Sjöqvist, Urban
    Karolinska Institutet, IBD-Unit at Karolinska University Hospital-Huddinge , Stockholm , Sweden.
    Lördal, Mikael
    Karolinska Institutet, IBD-Unit at Karolinska University Hospital-Huddinge , Stockholm , Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Department of Internal Medicine, Division of Gastroenterology,örebro University Hospital ,Örebro , Sweden.
    Lerm, Maria
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Söderholm, Johan D.
    Division of Surgery, Department of Clinical and Experimental Medicine, Linköping University , Linköping , Sweden.
    Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn's disease in Swedish men2009In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 5, p. 1180-1188Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Crohn's disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1beta. Production of mature IL-1beta is dependent on a caspase-1-activating protein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares structural similarities with Nod2, and both of these proteins are required for bacteria-induced IL-1beta secretion. The combination of the polymorphisms CARD8 (C10X)and NALP3 (Q705K) was recently shown to be associated with rheumatoid arthritis.Our aim was to investigate whether these combined polymorphisms play a role in the susceptibility to CD. METHODS: The study included 498 CD patients in two cohorts from different regions and 742 control individuals from a Swedish population. DNA was isolated from whole blood. Polymorphisms of (Q705K) NALP3 and (C10X) CARD8, as well as the Nod2 variants, R702W and G908R, were genotyped using the Taqman single nucleotide polymorphism assay. The Nod2 frameshift mutation, L1007fs, was detected by Megabace SNuPe genotyping. RESULTS: Our results show that men who have both the C10X and Q705K alleles in CARD8 and NALP3, and who express wild-type alleles of Nod2 are at an increased risk of developing CD (odds ratio, OR: 3.40 range: 1.32-8.76); P = 0.011). No association with these polymorphisms was found in women (OR: 0.89 (range: 0.44-1.77); P = 0.74). CONCLUSIONS: We suggest a role for combined polymorphisms in CARD8 and NALP3 in the development of CD in men, with obvious sex differences in the genetic susceptibility pattern. These findings give further support to the importance of innate immune responses in CD.

  • 17.
    Schoultz, Ida
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Verma, Deepti
    Törkvist, Leif
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Lerm, Maria
    Söderkvist, Peter
    Söderholm, Johan D.
    M2080 Compound Polymorphisms in CARD8 and CIAS1 Predispose to Crohn's Disease in a Swedish Cohort2008In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 134, no 4, p. A464-A465Article in journal (Other academic)
  • 18.
    Seibert, Volker
    et al.
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Prohl, Corinna
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Schoultz, Ida
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Rhee, Edward
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Lopez, Rebecca
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Abderazzaq, Kareem
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Zhou, Chunshui
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Wolf, Dieter A.
    Department of Cancer Cell Biology, Harvard School of Public Health, Boston, USA .
    Combinatorial diversity of fission yeast SCF ubiquitin ligases by homo- and heterooligomeric assemblies of the F-box proteins Pop1p and Pop2p2002In: BMC biochemistry, ISSN 1471-2091, Vol. 3, p. 1-15, article id 22Article in journal (Refereed)
    Abstract [en]

    Background: SCF ubiquitin ligases share the core subunits cullin 1, SKP1, and HRT1/RBX1/ROC1, which associate with different F-box proteins. F-box proteins bind substrates following their phosphorylation upon stimulation of various signaling pathways. Ubiquitin-mediated destruction of the fission yeast cyclin-dependent kinase inhibitor Rum1p depends on two heterooligomerizing F-box proteins, Pop1p and Pop2p. Both proteins interact with the cullin Pcu1p when overexpressed, but it is unknown whether this reflects their co-assembly into bona fide SCF complexes.

    Results: We have identified Psh1p and Pip1p, the fission yeast homologues of human SKP1 and HRT1/RBX1/ROC1, and show that both associate with Pop1p, Pop2p, and Pcu1p into a ~500 kDa SCFPop1p-Pop2p complex, which supports polyubiquitylation of Rum1p. Only the F-box of Pop1p is required for SCFPop1p-Pop2p function, while Pop2p seems to be attracted into the complex through binding to Pop1p. Since all SCFPop1p-Pop2p subunits, except for Pop1p, which is exclusively nuclear, localize to both the nucleus and the cytoplasm, the F-box of Pop2p may be critical for the assembly of cytoplasmic SCFPop2p complexes. In support of this notion, we demonstrate individual SCFPop1p and SCFPop2p complexes bearing ubiquitin ligase activity.

    Conclusion: Our data suggest that distinct homo- and heterooligomeric assemblies of Pop1p and Pop2p generate combinatorial diversity of SCFPop function in fission yeast. Whereas a heterooligomeric SCFPop1p-Pop2p complex mediates polyubiquitylation of Rum1p, homooligomeric SCFPop1p and SCFPop2p complexes may target unknown nuclear and cytoplasmic substrates.

  • 19.
    Wang, Arthur
    et al.
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Keita, Åsa V.
    Dept Surg, Cty Council Östergötland, Linköping, Sweden.
    Phan, Van
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    McKay, Catherine M.
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Schoultz, Ida
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Lee, Joshua
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Murphy, Michael P.
    MRC Mitochondrial Biol Unit, Cambridge, England.
    Fernando, Maria
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Ronaghan, Natalie
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Balce, Dale
    Joan Snyder Inst Chron Dis, Dept Comparat Biol & Expt Med, Fac Vet Med, Univ Calgary, Calgary AB, Canada.
    Yates, Robin
    Joan Snyder Inst Chron Dis, Dept Comparat Biol & Expt Med, Fac Vet Med, Univ Calgary, Calgary AB, Canada.
    Dicay, Michael
    Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, Canada.
    Beck, Paul L.
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, Canada.
    MacNaughton, Wallace K.
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Söderholm, Johan D.
    Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden; Dept Surg, Cty Council Östergötland, Linköping, Sweden .
    Mckay, Derek M.
    Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada.
    Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis2014In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 184, no 9, p. 2516-2527Article in journal (Refereed)
    Abstract [en]

    Epithelial permeability is often increased in inflammatory bowel diseases. We hypothesized that perturbed mitochondrial function would cause barrier dysfunction and hence epithelial mitochondria could be targeted to treat intestinal inflammation. Mitochondrial dysfunction was induced in human colon-derived epithelial cell lines or colonic biopsy specimens using dinitrophenol, and barrier function was assessed by transepithelial flux of Escherichia coil with or without mitochondria-targeted antioxidant (MTA) cotreatment. The impact of mitochondria-targeted antioxidants on gut permeability and dextran sodium sulfate (DSS)-induced colitis in mice was tested. Mitochondrial superoxide evoked by dinitrophenol elicited significant internalization and transtocation of E. coil across epithelia and control colonic biopsy specimens, which was more striking in Crohn's disease biopsy specimens; the mitochondria-targeted antioxidant, MitoTEMPO, inhibited these barrier defects. Increased gut permeability and reduced epithelial mitochondrial voltage-dependent anion channel expression were observed 3 days after DSS. These changes and the severity of DSS-colitis were reduced by MitoTEMPO treatment. In vitro DSS-stimulated IL-8 production by epithelia was reduced by MitoTEMPO. Metabolic stress evokes significant penetration of commensal bacteria across the epithelium, which is mediated by mitochondria-derived superoxide acting as a signaling, not a cytotoxic, molecule. MitoTEMPO inhibited this barrier dysfunction and suppressed colitis in DSS-colitis, likely via enhancing barrier function and inhibiting proinflammatory cytokine production. These novel findings support consideration of MTAs in the maintenance of epithelial barrier function and the management of inflammatory bowel diseases.

  • 20.
    Yakymenko, Olena
    et al.
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences. Department of Medical Sciences.
    Gullberg, Elisabeth
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Magnus
    Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden.
    Almer, Sven
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden; GastroCentrum, Karolinska University Hospital, Stockholm, Sweden.
    Wallon, Conny
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Wang, Arthur
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    Keita, Åsa V.
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Campbell, Barry J.
    Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK.
    McKay, Derek M.
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    Söderholm, Johan D.
    Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 677-684Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Infliximab is important in the therapeutic arsenal of Crohn's disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.

    MATERIALS AND METHODS: Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.

    RESULTS: Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8-1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.

    CONCLUSION: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab's clinical efficacy in colonic CD.

  • 21.
    Zurek, Birte
    et al.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Schoultz, Ida
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Neerincx, Andreas
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Napolitano, Luisa M.
    Cluster in Biomedicine (CBM), AREA Science Park, Trieste, Italy; Telethon Institute of Genetics and Medicine, Naples, Italy.
    Birkner, Katharina
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Bennek, Eveline
    Department of Medicine III, University Hospital Aachen, Aachen, Germany.
    Sellge, Gernot
    Department of Medicine III, University Hospital Aachen, Aachen, Germany.
    Lerm, Maria
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Meroni, Germana
    Cluster in Biomedicine (CBM), AREA Science Park, Trieste, Italy.
    Söderholm, Johan D.
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Kufer, Thomas A.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, article id e41255Article in journal (Refereed)
    Abstract [en]

    NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohn's disease. We found that TRIM27 expression is increased in Crohn's disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus.We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.

  • 22.
    Östlund-Lagerström, Lina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Blomberg, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Algilani, Samal
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Schoultz, Magnus
    Nutrition and Physical Activity Research Centre, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Kihlgren, Annica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert J.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Schoultz, Ida
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Senior orienteering athletes as a model of healthy aging: a mixed-method approach2015In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 15, article id 76Article in journal (Refereed)
    Abstract [en]

    Background: The proportion of individuals reaching an old age is increasing and will, in the near future consume a majority of health care resources. It is therefore essential to facilitate the maintenance of optimal functionality among older adults. By characterizing older individuals experiencing wellbeing, factors important to promote and maintain health through life can be identified. Orienteering is an endurance-running sport involving cross-country navigation, demanding both cognitive and physical skills of its practitioners. In this study we aim to explore a Swedish population of senior orienteering athletes as a potential model of healthy aging.

    Methods: We undertook a mixed-method approach using quantitative (i.e. questionnaires) and qualitative (i.e. focus group discussions) methodologies to explore a population of senior orienteering athletes (n = 136, median age = 69 (67-71) years). Quantitative data was collected to evaluate health status, assessing physical activity (Frandin-Grimby activity scale (FGAS)), functional wellbeing (EQ-5D-5 L), gut health (Gastrointestinal symptoms rating scale (GSRS)), anxiety and depression (Hospital Anxiety and Depression scale (HADS)) and overall health (Health index (HI)). The data was further compared to reference values obtained from a free-living Swedish population of older adults. Focus group discussions (FGD) were performed as a complement to the quantitative data to facilitate the individuals' own views on health and physical activity.

    Results: The orienteering athletes enrolled in the study reported a significantly better health compared to the free-living older adults (p < 0.0015) on all questionnaires except HADS. The high health status displayed in this population was further confirmed by the FGD findings, in which all participants declared their engagement in orienteering as a prerequisite for health.

    Conclusions: In conclusion our results show that senior orienteering may represent an ideal model in studies of healthy aging. Furthermore, our results show that even though the senior orienteering athletes are well aware of the long-term benefits of physical activity and have practiced the sport from a young age, they particularly point out that their engagement in orienteering is driven by short-term values such as enjoyment and passion. This may be important to consider when introducing public health interventions among the general older population.

  • 23.
    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)
  • 24.
    Östlund-Lagerström, Lina
    et al.
    Örebro University, School of Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Probiotic administration among free-living older adults: a double blinded, randomised, placebo-controlled clinical trialManuscript (preprint) (Other academic)
  • 25.
    Östlund-Lagerström, Lina
    et al.
    Nutrition and Physical Activity Research Centre, Örebro University, Örebro, Sweden; Nutrition Gut Brain Interactions Research Centre, School of Health and Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden.
    Kihlgren, Annica
    Örebro University, School of Health Sciences. Nutrition and Physical Activity Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Björkstén, Bengt
    Nutrition and Physical Activity Research Centre, Örebro University, Örebro, Sweden; Nutrition Gut Brain Interactions Research Centre, School of Health and Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden; Institute of Environmental Medicine, Karolinska institutet, Stockholm, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences. Nutrition and Physical Activity Research Centre, Örebro University, Örebro, Sweden; Nutrition Gut Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Probiotic administration among free-living older adults: a double blinded, randomized, placebo-controlled clinical trial2016In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 15, article id 80Article in journal (Refereed)
    Abstract [en]

    Background: Diseases of the digestive system have been found to contribute to a higher symptom burden in older adults. Thus, therapeutic strategies able to treat gastrointestinal discomfort might impact the overall health status and help older adults to increase their overall health status and optimal functionality.

    Objective: The aim of this double-blinded, randomized, placebo-controlled clinical trial was to evaluate the effect of the probiotic strain Lactobacillus reuteri on digestive health and wellbeing in older adults.

    Methods: The study enrolled general older adults (>65 years). After eligibility screening qualified subjects (n = 290) participated in a 2-arm study design, with each arm consisting of 12 weeks of intervention of either active or placebo product. Primary outcome measure was set to changes in gastrointestinal symptoms and secondary outcome measures were changes in level of wellbeing, anxiety and stress. Follow up was performed at 8 and 12 weeks.

    Results: No persistent significant effects were observed on the primary or secondary outcome parameters of the study. A modest effect was observed in the probiotic arm, were levels of stress decreased at week 8 and 12. Similarly, we found that subjects suffering from indigestion and abdominal pain, respectively, showed a significant decrease of anxiety at week 8 after probiotic treatment, but not at week 12.

    Conclusion: The RCT failed to show any improvement in digestive health after daily intake of a probiotic supplement containing L. reuteri. Neither was any significant improvement in wellbeing, stress or anxiety observed. Even though the RCT had a negative outcome, the study highlights issues important to take into consideration when designing trials among older adults.

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