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Ganda Mall, J.-P., Östlund-Lagerström, L., Lindqvist, C. M., Algilani, S., Rasoal, D., Repsilber, D., . . . Schoultz, I. (2018). Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?. BMC Geriatrics, 18(1), Article ID 75.
Open this publication in new window or tab >>Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
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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: 2018-08-20Bibliographically approved
Björkqvist, O., Repsilber, D., Seifert, M., Engstrand, L., Rangel, I. & Halfvarson, J. (2018). Increasing abundance of faecalibacterium prausnitzii is associated with decreased intestinal inflammation in Crohn's disease: A longitudinal study. Journal of Crohn's & Colitis, 12(Suppl. 1), S468-S469
Open this publication in new window or tab >>Increasing abundance of faecalibacterium prausnitzii is associated with decreased intestinal inflammation in Crohn's disease: A longitudinal study
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S468-S469Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66747 (URN)000427318902090 ()
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-08-31Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved
Drobin, K., Assadi, G., Hong, M.-G., Andersson, E., Fredolini, C., Forsström, B., . . . Halfvarson, J. (2018). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases
Open this publication in new window or tab >>Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
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2018 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

Place, publisher, year, edition, pages
Lippincott-Raven Publishers, 2018
Keywords
inflammatory bowel disease, affinity proteomics, LACC1
National Category
Gastroenterology and Hepatology Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-69892 (URN)10.1093/ibd/izy326 (DOI)30358838 (PubMedID)
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2018-11-08Bibliographically approved
Gorreja, F., Rush, S., Marques, T. M., Repsilber, D., Baker, A., Wall, R. & Brummer, R. J. (2018). The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function. In: : . Paper presented at Food and Inflammation - 2nd Conference of Food Science Sweden, Örebro, Sweden, 21 Nov., 2018.
Open this publication in new window or tab >>The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function
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2018 (English)Conference paper, Oral presentation only (Other academic)
Keywords
Probiotics, Inflammation, Prebiotics, Immune system, Dietary
National Category
Medical and Health Sciences Microbiology
Research subject
Molecular Biology; Medicine; Microbiology
Identifiers
urn:nbn:se:oru:diva-70257 (URN)
Conference
Food and Inflammation - 2nd Conference of Food Science Sweden, Örebro, Sweden, 21 Nov., 2018
Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-22Bibliographically approved
Holster, S., Brummer, R. J., Repsilber, D. & König, J. (2017). Faecal microbiota transfer in irritable bowel syndrome – clinical outcomes of a randomised placebo- controlled trial. In: : . Paper presented at United European Gastroenterology (UEG) Week, Barcelona (Oct 28-Nov 1, 2017) (pp. A155-A156).
Open this publication in new window or tab >>Faecal microbiota transfer in irritable bowel syndrome – clinical outcomes of a randomised placebo- controlled trial
2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-66283 (URN)10.1177/2050640617725668 (DOI)000403140300297 ()
Conference
United European Gastroenterology (UEG) Week, Barcelona (Oct 28-Nov 1, 2017)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-09Bibliographically approved
Holster, S., Brummer, R. J., Repsilber, D. & König, J. (2017). Fecal Microbiota Transplantation in Irritable Bowel Syndrome – A randomized placebo- controlled trial. In: : . Paper presented at Digestive Disease Week (DDW), Chicago, IL, USA (May 6-9, 2017) (pp. S101-S102). , 152(5)
Open this publication in new window or tab >>Fecal Microbiota Transplantation in Irritable Bowel Syndrome – A randomized placebo- controlled trial
2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-66294 (URN)10.1016/S0016-5085(17)30679-0 (DOI)000403140300297 ()
Conference
Digestive Disease Week (DDW), Chicago, IL, USA (May 6-9, 2017)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-09Bibliographically approved
Gunaltay, S., Repsilber, D., Helenius, G., Nyhlin, N., Bohr, J., Hultgren, O. & Hultgren Hörnquist, E. (2017). Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis. Inflammatory Bowel Diseases, 23(6), 932-945
Open this publication in new window or tab >>Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
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2017 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed) Published
Abstract [en]

Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
Keywords
collagenous colitis, lymphocytic colitis, next-generation sequencing, ulcerative colitis, T-cell repertoire analysis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-59319 (URN)10.1097/MIB.0000000000001127 (DOI)000405609200014 ()28498152 (PubMedID)2-s2.0-85019705487 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation)  SLS-176271/2011  98031/2010 

Örebro University Hospital Research Foundation (Nyckelfonden)  

Research Committee, Örebro County Council  

Örebro University 

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2018-09-04Bibliographically approved
Andersson, E., Bergemalm, D., Kruse, R., Neumann, G., D'Amato, M., Repsilber, D. & Halfvarson, J. (2017). Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles. PLoS ONE, 12(10), Article ID e0186142.
Open this publication in new window or tab >>Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186142Article in journal (Refereed) Published
Abstract [en]

Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.

Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.

Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.

Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-61928 (URN)10.1371/journal.pone.0186142 (DOI)000412360300129 ()28982144 (PubMedID)2-s2.0-85030719034 (Scopus ID)
Funder
Swedish Foundation for Strategic Research , RB13-016Swedish Research Council, 521-2011-2764
Note

Funding Agency:

Örebro University Hospital Research Foundation  OLL-507001  OLL-526131

Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2018-08-07Bibliographically approved
Koskela von Sydow, A., Janbaz, C., Kardeby, C., Repsilber, D. & Ivarsson, M. (2016). IL-1α Counteract TGF-β Regulated Genes and Pathways in Human Fibroblasts. Journal of Cellular Biochemistry, 117(7), 1622-1632
Open this publication in new window or tab >>IL-1α Counteract TGF-β Regulated Genes and Pathways in Human Fibroblasts
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2016 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 117, no 7, p. 1622-1632Article in journal (Refereed) Published
Abstract [en]

Dysregulated wound healing is commonly associated with excessive fibrosis. Connective tissue growth factor (CTGF/CCN2) is characteristically overexpressed in fibrotic diseases and stimulated by transforming growth factor-β (TGF-β) in dermal fibroblasts. We previously showed that interleukin-1 (IL-1α) counteracts TGF-β-stimulated CTGF mRNA and protein expression in these cells. The aim of this study was to explore the effects of IL-1α on further genes and pathways in TGF-β regulated fibroblasts. Transcriptional microarray and multiple comparison analysis showed that the antagonizing effects of IL-1α was much more prominent than the synergistic effects, both with respect to number of genes and extent of changes in gene expression. Moreover, comparing canonical pathways by gene set enrichment analysis and the Ingenuity Pathway Analysis tool revealed that IL-1α counteracted TGF-β in the top six most confident pathways regulated by both cytokines. Interferon and IL-1 signaling, as well as two pathways involved in apoptosis signaling were suppressed by TGF-β and activated by IL-1α. Pathways involving actin remodeling and focal adhesion dynamics were activated by TGF-β and suppressed by IL-1α. Analyzing upstream regulators in part corroborate the comparison of canonical pathways and added cell cycle regulators as another functional group regulated by IL-1α. Finally, gene set enrichment analysis of fibrosis-related genes indicated that IL-1 moderately counteracts the collective effect of TGF-β on these genes. Microarray results were validated by qPCR. Taken together, the results indicate prominent antagonistic effects of IL-1α on TGF-β regulated interferon signaling, as well as on a wide variety of other genes and pathways in fibroblasts. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2016
Keywords
Connective tissue growth factor, transforming growth factor-beta, interleukin-1, interferon, fibroblast, fibrosis and ingenuity pathway analysis
National Category
Other Basic Medicine Cell Biology Biochemistry and Molecular Biology
Research subject
Cell Research
Identifiers
urn:nbn:se:oru:diva-48463 (URN)10.1002/jcb.25455 (DOI)000375916800014 ()26629874 (PubMedID)2-s2.0-84964773875 (Scopus ID)
Note

Funding Agencies:

Örebro County Council Research Committee of the Örebro University Hospital OLL-550071

Nyckelfonden AE56340

Available from: 2016-02-22 Created: 2016-02-22 Last updated: 2018-09-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7173-5579

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