oru.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 103) Show all publications
Drobin, K., Assadi, G., Hong, M.-G., Andersson, E., Fredolini, C., Forsström, B., . . . Halfvarson, J. (2019). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases, 25(2), 306-316
Open this publication in new window or tab >>Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
Show others...
2019 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed) Published
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, 2019
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: 2019-01-14Bibliographically approved
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?
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: 2018-08-20Bibliographically approved
Rush, S. & Repsilber, D. (2018). Capturing context-specific regulation in molecular interaction networks. BMC Bioinformatics, 19(1), Article ID 539.
Open this publication in new window or tab >>Capturing context-specific regulation in molecular interaction networks
2018 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 19, no 1, article id 539Article in journal (Refereed) Published
Abstract [en]

Background: Molecular profiles change in response to perturbations. These changes are coordinated into functional modules via regulatory interactions. The genes and their products within a functional module are expected to be differentially expressed in a manner coherent with their regulatory network. This perspective presents a promising approach to increase precision in detecting differential signals as well as for describing differential regulatory signals within the framework of a priori knowledge about the underlying network, and so from a mechanistic point of view.

Results: We present Coherent Network Expression (CoNE), an effective procedure for identifying differentially activated functional modules in molecular interaction networks. Differential gene expression is chosen as example, and differential signals coherent with the regulatory nature of the network are identified. We apply our procedure to systematically simulated data, comparing its performance to alternative methods. We then take the example case of a transcription regulatory network in the context of particle-induced pulmonary inflammation, recapitulating and proposing additional candidates to previously obtained results. CoNE is conveniently implemented in an R-package along with simulation utilities.

Conclusion: Combining coherent interactions with error control on differential gene expression results in uniformly greater specificity in inference than error control alone, ensuring that captured functional modules constitute real findings.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Activated subnetwork, Coherent differential expression, Differential regulation, Error control, Functional module, Molecular network
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:oru:diva-65214 (URN)10.1186/s12859-018-2513-7 (DOI)000454209300003 ()30577761 (PubMedID)2-s2.0-85058920164 (Scopus ID)
Funder
Knowledge Foundation, 20110225
Available from: 2018-02-24 Created: 2018-02-24 Last updated: 2019-01-11Bibliographically 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
Show others...
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
Show others...
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
Neumann, G., Wall, R., Rangel, I., Marques, T. M. & Repsilber, D. (2018). Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability. BMC Systems Biology, 12(1), Article ID 144.
Open this publication in new window or tab >>Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability
Show others...
2018 (English)In: BMC Systems Biology, ISSN 1752-0509, E-ISSN 1752-0509, Vol. 12, no 1, article id 144Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties.

RESULTS: We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed.

CONCLUSIONS: Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Bi-stability, Butyrate, Dynamical model, Dysbiosis, Gut microbiome, Inflammation, Short chain fatty acids
National Category
Gastroenterology and Hepatology Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:oru:diva-70827 (URN)10.1186/s12918-018-0667-6 (DOI)000453547300001 ()30558589 (PubMedID)2-s2.0-85058628095 (Scopus ID)
Funder
Knowledge Foundation, 20110225
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-01-08Bibliographically 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
Show others...
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)
Conference
United European Gastroenterology (UEG) Week, Barcelona (Oct 28-Nov 1, 2017)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-02-01Bibliographically 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
Show others...
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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7173-5579

Search in DiVA

Show all publications