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  • 1.
    Sjödahl, Jenny
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ingemansson, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Bureychak, Tetyana
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Norlin, Anna-Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Mantorp. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Olsen Faresjö, Åshild
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Defecation symptoms in primary health care patients with irritable bowel syndrome2024In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 59, no 1, p. 16-24Article in journal (Refereed)
    Abstract [en]

    Background: The objectives of the present study were to (a) measure the prevalence of defecation symptoms in IBS, (b) investigate the relationship between stool consistency and defecation symptoms in IBS, and (c) investigate the association of defecation symptoms with health-related quality of life (HRQL) and self-reported stress in patients with IBS cared for in a primary health care setting. Methods: Ten primary health care centres joined the study. 282 patients with IBS as well as 372 non-IBS controls filled in gastrointestinal symptom diaries prospectively for two weeks as well as the Perceived Stress Scale-14 (PSS14) and the EuroQol barometer to measure perceived stress and HRQL, respectively. Results: Incomplete evacuation was present in 51% vs. 21% of the stools among the IBS patients and the non-IBS controls, respectively. The need to strain during defecation was existing in 41% vs. 33% of the stools for the IBS patients and the non-IBS controls, respectively. Urgency was experienced in 37% of the stools in the IBS patients compared with 18% of the stools in the non-IBS controls. Patients with IBS experienced in a significant higher degree of overlapping symptoms per stool (p < 0.001 to p = 0.007). The occurrence of all defecation symptoms in the same patient was related to decreased HRQL, and increased stress (p = 0.001 to p < 0.001). Conclusions: An overlap between IBS and symptoms from the anorectal region related to defecation was found in a primary health care population. Defecation symptoms are very common in primary care IBS-patients, it co-occurs with increased self-perceived stress, and decreased HRQL.

    The full text will be freely available from 2024-08-23 00:00
  • 2.
    Gerdin, Linda
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Surg Clin Jonkoping Cty, Sweden.
    Gonzalez-Castro, Ana M.
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Persborn, Mats
    Surg Clin Jonkoping Cty, Sweden.
    Santos, Javier
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain.
    Walter, Susanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Vicario, Maria
    Univ Autonoma Barcelona, Spain; Univ Autonoma Barcelona, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Nestle Res Soc Prod Nestle SA, Switzerland.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers2023In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 11, no 1, p. 31-41Article in journal (Refereed)
    Abstract [en]

    Background Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. Objective To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress-induced molecular events in the rectal mucosa under healthy conditions. Methods Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real-time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Results Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress-induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down-regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2 expression. Conclusion Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress-mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.

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  • 3.
    Bednarska, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Biskou, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Israelsen, Hans
    Nord Rebalance AS, Denmark.
    Tinnerfelt Winberg, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome2022In: Frontiers in Nutrition, E-ISSN 2296-861X, Vol. 9, article id 1004084Article in journal (Refereed)
    Abstract [en]

    Background: Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm (R)( ), also called Profermin (R), is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this study, we investigated whether ReFerm (R) has a beneficial effect on the intestinal epithelial barrier function in patients with IBS.Materials and methods: Thirty patients with moderate to severe IBS-diarrhoea (IBS-D) or IBS-mixed (IBS-M) were treated with enema containing ReFerm (R) or placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of treatment with ReFerm (R) or placebo twice daily. The biopsies were mounted in Ussing chambers, and paracellular and transcellular permeabilities were measured for 120 min. In addition, the effects of ReFerm (R) or placebo on the epithelial barrier were investigated in vitro using Caco-2 cells.Results: ReFerm (R) reduced paracellular permeability (p < 0.05) and increased transepithelial resistance (TER) over time (p < 0.01), whereas the placebo had no significant effect in patients. In ReFerm (R)-treated Caco-2 cells, paracellular and transcellular permeabilities were decreased compared to the control (p < 0.05) and placebo (p < 0.01). TER was increased in Caco-2 ReFerm (R)-treated cells, and normalised TER was increased in ReFerm (R)-treated Caco-2 cells compared to control (p < 0.05) and placebo-treated (p < 0.05) cells.Conclusion: ReFerm (R) significantly reduced paracellular permeability and improved TER in colonic biopsies collected from patients with IBS and in a Caco-2 cell model. Our results offer new insights into the potential benefits of ReFerm (R) in IBS management. Further studies are needed to identify the molecular mechanisms underlying the barrier-protective properties of ReFerm (R).

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  • 4.
    Casado Bedmar, Maria Teresa
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Meira de Faria, Felipe
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Biskou, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Lindqvist, Carl Mårten
    Orebro Univ, Sweden.
    Ranasinghe, Purnika Damindi
    Queens Univ Belfast, North Ireland.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Peterson, Christer
    Uppsala Univ, Sweden; Diagnost Dev, Sweden.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Carlson, Marie
    Uppsala Univ, Sweden.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS - A possible association with microbiota?2022In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 111, no 3, p. 655-665Article in journal (Refereed)
    Abstract [en]

    Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.

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  • 5.
    Biskou, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Meira de Faria, Felipe
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Tinnerfelt Winberg, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Increased Numbers of Enteric Glial Cells in the Peyers Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohns Disease2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 3, article id 335Article in journal (Refereed)
    Abstract [en]

    Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohns disease (CD) is elusive. Microscopic erosions over the ileal Peyers patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyers patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyers patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyers patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyers patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.

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  • 6.
    Barazanji, Nawroz
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Hamilton, Paul J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Ruhr University Bochum, Bochum, Germany.
    Simon, Rozalyn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Tapper, Sofie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Tisell, Anders
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Lundberg, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms2022In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 35, article id 103128Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC.

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  • 7.
    Bureychak, Tetyana
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen Faresjö, Åshild
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Sjödahl, Jenny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Norlin, Anna-Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Mantorp.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Symptoms and health experience in irritable bowel syndrome with focus on men2022In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 34, no 11, article id e14430Article in journal (Refereed)
    Abstract [en]

    Background Irritable bowel syndrome (IBS) is a disorder with a predominance in women; IBS in men is less studied. The present study evaluated symptoms as well as health and social experiences of men with IBS. Methods This cross-sectional study included 293 patients with IBS (64 men) and 363 non-IBS controls (62 men). Gastrointestinal symptom diaries were filled in prospectively, and data on comorbidities and healthcare-seeking behavior were assessed by questionnaires. Men with IBS were compared with men without IBS and women with IBS. Key results Compared with women with IBS, men with IBS had fewer contacts with the healthcare system, fewer psychiatric comorbidities, fewer sleeping problems, and less chronic pain. Urgency to defecate and nausea were less common, and stool frequency was higher in men with IBS. There was no difference between men with and without IBS in terms of educational level, satisfaction with household economy, or living with a partner. In contrast, women with IBS more often lived alone, were more often dissatisfied with household economy, and had a lower educational level than women without IBS. Men with IBS had the same proportion of full-time employment as men without IBS but in contrast, the proportion of women with IBS in full-time employment was only 34%, compared to 50% of the women without IBS. Conclusion and inferences The present study improves the understanding of mens experiences of IBS and suggests that sex and gender may be integrated into the biopsychosocial model of IBS.

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  • 8.
    Meira de-Faria, Felipe
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Casado-Bedmar, Maite
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Lindqvist, Carl Marten
    Orebro Univ, Sweden.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Altered interaction between enteric glial cells and mast cells in the colon of women with irritable bowel syndrome2021In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 33, no 11, article id e14130Article in journal (Refereed)
    Abstract [en]

    Background Enteric glial cells (EGC) and mast cells (MC) are intimately associated with gastrointestinal physiological functions. We aimed to investigate EGC-MC interaction in irritable bowel syndrome (IBS), a gut-brain disorder linked to increased intestinal permeability, and MC. Methods Parallel approaches were used to quantify EGC markers in colonic biopsies from healthy controls (HC) and patients with IBS. Data were correlated with MC, vasoactive intestinal polypeptide (VIP) and VIP receptors (VPAC1/VPAC2) expressions, and bacterial translocation through biopsies mounted in Ussing chambers. In addition, we investigated the effects of EGC mediators on colonic permeability and the pharmacological-induced responses of EGC and MC cell lines. Key Results Immunofluorescence of IBS colonic mucosa, as well as Western blotting and ELISA of IBS biopsy lysates, revealed increased glial fibrillary intermediate filament (GFAP) expression, indicating EGC activation. Mucosal GFAP correlated with increased MC and VPAC1(+)MC numbers and decreased VIP+MC, which seemed to control bacterial translocation in HC. In the contrary, EGC activation in IBS correlated with less MC and VPAC1(+) MC numbers, and more VIP+ MC. In vitro, MC and EGC cell lines showed intracellular calcium responses to each others mediators. Furthermore, EGC mediators prevented VIP-induced MC degranulation, while MC mediators induced a reactive EGC phenotype. In Ussing chambers, EGC mediators decreased paracellular passage through healthy colonic biopsies. Conclusions & Inferences Findings suggest the involvement of EGC and MC in the control of barrier function in the human colon and indicate a potential EGC-MC interaction that seems altered in IBS, with detrimental consequences to colonic permeability. Altogether, results suggest that imbalanced EGC-MC communication contributes to the pathophysiology of IBS.

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  • 9.
    Jones, Michael P.
    et al.
    Macquarie Univ, Australia.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Talley, Nicholas J.
    Univ Newcastle, Australia.
    Walker, Marjorie M.
    Univ Newcastle, Australia.
    Holtmann, Gerald J.
    Princess Alexandra Hosp, England.
    Shah, Ayesha
    Princess Alexandra Hosp, England.
    DAmato, Mauro
    CIC BioGUNE BRTA, Spain.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Andreasson, Anna
    Stockholm Univ, Sweden.
    Clusters of community-dwelling individuals empirically derived from stool diaries correspond with clinically meaningful outcomes2021In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 33, no 1S, p. E740-E745Article in journal (Refereed)
    Abstract [en]

    Background

    Functional gastrointestinal disorders (FGIDs) are diagnosed according to expert consensus criteria based on recall of symptoms over periods of 3 months or longer. Whether the expert opinion concords with underlying disease process and whether individual recall is accurate are both in doubt. This study aimed to identify naturally occurring clusters of individuals with respect to symptom pattern, evaluate their significance, compare cluster profiles with expert opinion and evaluate their temporal stability.

    Methods

    As part of a random population study of FGID-related symptoms, we first explored the use of prospective stool and symptom diaries combined with empirical grouping of individuals into clusters using nonhierarchical cluster analysis.

    Results

    The analysis identified two clusters of individuals, one of which was characterized by elevated scores on all domains of symptoms (26% of the sample) and one that was low to average on all domains (74% of the sample). Cluster membership was found to be stable over a long interval. Clusters were found to differ on most domains of quality-of-life (d = 0.46-0.74), self-rated health (d = -0.42) and depression (d = -0.42) but not anxiety. Prevalence of clinically diagnosed irritable bowel syndrome (IBS) was higher in the more impacted cluster (33%) compared with the healthy cluster (13%; P < 0.0001).

    Conclusion

    A naturalistic classification of individuals challenges consensus criteria in showing that some IBS individuals have a symptom experience not unlike health. The proposed approach has demonstrated temporal stability over time, unlike consensus criteria. A naturalistic disease classification system may have practical advantages over consensus criteria when supported by a decision-analytic system. Copyright (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.

  • 10.
    Meira de Faria, Felipe
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ström, Magnus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Colonic paracellular permeability and circulating zonulin-related proteins2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 4, p. 424-431Article in journal (Refereed)
    Abstract [en]

    Objective Irritable bowel syndrome (IBS) is a gut-brain disorder associated with increased gut permeability. Zonulin has been suggested to regulate the gut barrier and claimed to be pre-haptoglobin 2 (pre-HP2) and circulating zonulin is often used as a proxy for gastrointestinal permeability. This study investigated the correlation between colonic paracellular permeability and levels of circulating zonulin and pre-HP2. Materials and Methods Colonic biopsies from 32 patients with IBS and 15 healthy controls (HC) were used to measure permeability in Ussing chambers and levels of zonulin (Cusabio ELISA). Zonulin was also measured in blood samples from 40 HC, 78 patients with IBS and 20 patients with celiac disease (CeD), before and after a gluten-free diet. In addition, we verified HP genotype and circulating pre-HP2 using a monoclonal pre-HP2 antibody (Bio-Rad) by ELISA. Results Increased colonic paracellular permeability correlated positively with zonulin levels in IBS biopsies, but negatively with plasma zonulin. We found no agreement between circulating zonulin and pre-HP2. Genotyping revealed non-specificity of the zonulin kit, as all pre-HP2 non-producers presented detectable levels. Patients with CeD displayed higher pre-HP2 and zonulin levels compared to HC. A gluten-free diet in patients with CeD led to lower serum zonulin and pre-HP2 concentrations. Conclusions Our study suggests that neither circulating zonulin nor pre-HP2 mirror colonic permeability. Our data corroborate previous reports showing the inability of the Cusabio zonulin kit to target zonulin and highlights that the results of studies using this kit must be re-examined with caution.

  • 11.
    Norlin, Anna-Karin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Mantorp.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Icenhour, Adriane
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Keita, Åsa
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Elsenbruch, Sigrid
    Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Jones, Michael P.
    Department of Psychology, Macquarie University, Sydney, Australia.
    Simon, Rozalyn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fatigue in irritable bowel syndrome is associated with plasma levels of TNF-α and mesocorticolimbic connectivity2021In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 92, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a symptom-based disorder of gut-brain interactions generating abdominal pain. It is also associated with a vulnerability to develop extraintestinal symptoms, with fatigue often reported as one of the most disturbing. Fatigue is related to brain function and inflammation in several disorders, however, the mechanisms of such relations in IBS remain elusive. This study aimed to elucidate fatigue and its association with a resting state network of mesocorticolimbic regions of known importance in fatigue, and to explore the possible role of circulating TNF-α levels in IBS and healthy controls (HC). Resting state functional magnetic resonance imaging (fMRI) was conducted in 88 IBS patients and 47 HC of similar age and gender to investigate functional connectivity between mesocorticolimbic regions. Further, fatigue impact on daily life and plasma levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α), of known relevance to immune activation in IBS, were also measured. The selected mesocorticolimbic regions indeed formed a functionally connected network in all participants. The nucleus accumbens (NAc), in particular, exhibited functional connectivity to all other regions of interest. In IBS, fatigue impact on daily life was negatively correlated with the connectivity between NAc and dorsolateral prefrontal cortex bilaterally (left p = 0.019; right p = 0.038, corrected for multiple comparisons), while in HC, fatigue impact on daily life was positively correlated to the connectivity between the right NAc and anterior middle insula in both hemispheres (left p = 0.009; right p = 0.011). We found significantly higher levels of TNF-α in IBS patients compared to HC (p = 0.001) as well as a positive correlation between TNF-α and fatigue impact on daily life in IBS patients (rho = 0.25, p = 0.02) but not in HC (rho = −0.13, p = 0.37). There was no association between functional connectivity in the mesocorticolimbic network and plasma levels of TNF-α in either group In summary, this novel multimodal study provides the first evidence that the vulnerability to fatigue in IBS is associated with connectivity within a mesocorticolimbic network as well as immune activation. These findings warrant further investigation, both peripherally and potentially with measurements of central immune activation as well.

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  • 12.
    Bonfiglio, Ferdinando
    et al.
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Liu, Xingrong
    Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Smillie, Christopher
    Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
    Pandit, Anita
    Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
    Kurilshikov, Alexander
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Bacigalupe, Rodrigo
    Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven 3000, Belgium.
    Zheng, Tenghao
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nim, Hieu
    School of Biological Sciences, Monash University, Clayton, VIC, Australia.
    Garcia-Etxebarria, Koldo
    Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain.
    Bujanda, Luis
    Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universidad del País Vasco (UPV/EHU), San Sebastian, Spain.
    Andreasson, Anna
    Division of Clinical Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Agreus, Lars
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Abecasis, Gonçalo
    Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
    Eijsbouts, Chris
    Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
    Jostins, Luke
    Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK; Christ Church, University of Oxford, Oxford, UK.
    Parkes, Miles
    Division of Gastroenterology, Department of Medicine, University of Cambridge, Cambridge, UK.
    Hughes, David A
    MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Timpson, Nicholas
    MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Raes, Jeroen
    Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven 3000, Belgium.
    Franke, Andre
    Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Kennedy, Nicholas A
    IBD Pharmacogenetics, College of Medicine and Health, University of Exeter, Exeter, UK.
    Regev, Aviv
    Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
    Zhernakova, Alexandra
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Simren, Magnus
    Dept of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Camilleri, Michael
    Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
    DAmato, Mauro
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.
    GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome2021In: Cell Genomics, E-ISSN 2666-979X, Vol. 1, no 3, article id 100069Article in journal (Refereed)
    Abstract [en]

    Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.

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  • 13.
    Kurilshikov, Alexander
    et al.
    Univ Groningen, Netherlands.
    Medina-Gomez, Carolina
    Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands.
    Bacigalupe, Rodrigo
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Radjabzadeh, Djawad
    Erasmus MC Univ Med Ctr, Netherlands.
    Wang, Jun
    Katholieke Univ Leuven, Belgium; VIB, Belgium; Chinese Acad Sci, Peoples R China.
    Demirkan, Ayse
    Univ Groningen, Netherlands; Univ Surrey, England.
    Le Roy, Caroline I
    Kings Coll London, England.
    Garay, Juan Antonio Raygoza
    Univ Toronto, Canada; Mt Sinai Hosp, Canada.
    Finnicum, Casey T.
    Avera McKennan Hosp, SD USA; Univ Hlth Ctr, SD USA.
    Liu, Xingrong
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Zhernakova, Daria V
    Univ Groningen, Netherlands; ITMO Univ, Russia.
    Bonder, Marc Jan
    Univ Groningen, Netherlands.
    Hansen, Tue H.
    Univ Copenhagen, Denmark.
    Frost, Fabian
    Univ Med Greifswald, Germany.
    Ruhlemann, Malte C.
    Christian Albrechts Univ Kiel, Germany.
    Turpin, Williams
    Univ Toronto, Canada; Mt Sinai Hosp, Canada.
    Moon, Jee-Young
    Albert Einstein Coll Med, NY 10467 USA.
    Kim, Han-Na
    Sungkyunkwan Univ, South Korea; Sungkyunkwan Univ, South Korea.
    Lull, Kreete
    Univ Tartu, Estonia.
    Barkan, Elad
    Weizmann Inst Sci, Israel.
    Shah, Shiraz A.
    Copenhagen Univ Hosp, Denmark.
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, TX 77030 USA.
    Szopinska-Tokov, Joanna
    Univ Texas Hlth Sci Ctr Houston, TX USA; Radboudumc, Netherlands.
    Wallen, Zachary D.
    Univ Alabama Birmingham, AL 35294 USA.
    Borisevich, Dmitrii
    Univ Copenhagen, Denmark.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Andreasson, Anna
    Stockholm Univ, Sweden.
    Bang, Corinna
    Christian Albrechts Univ Kiel, Germany.
    Bedrani, Larbi
    Univ Toronto, Canada.
    Bell, Jordana T.
    Kings Coll London, England.
    Bisgaard, Hans
    Copenhagen Univ Hosp, Denmark.
    Boehnke, Michael
    Univ Michigan, MI 48109 USA.
    Boomsma, Dorret I
    Vrije Univ, Netherlands.
    Burk, Robert D.
    Albert Einstein Coll Med, NY 10467 USA.
    Claringbould, Annique
    Univ Groningen, Netherlands.
    Croitoru, Kenneth
    Univ Toronto, Canada; Mt Sinai Hosp, Canada.
    Davies, Gareth E.
    Avera McKennan Hosp, SD USA; Univ Hlth Ctr, SD USA; Vrije Univ, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC Univ Med Ctr, Netherlands; Univ Oxford, England.
    Duijts, Liesbeth
    Erasmus MC Univ Med Ctr, Netherlands.
    Falony, Gwen
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Fu, Jingyuan
    Univ Groningen, Netherlands.
    van der Graaf, Adriaan
    Univ Groningen, Netherlands.
    Hansen, Torben
    Univ Copenhagen, Denmark.
    Homuth, Georg
    Univ Med Greifswald, Germany.
    Hughes, David A.
    Univ Bristol, England; Univ Bristol Sch Med, England.
    Ijzerman, Richard G.
    Amsterdam Univ Med Ctr, Netherlands.
    Jackson, Matthew A.
    Kings Coll London, England; Univ Oxford, England.
    Jaddoe, Vincent W. V.
    Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands.
    Joossens, Marie
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Jorgensen, Torben
    Univ Copenhagen, Denmark; Univ Copenhagen, Denmark.
    Keszthelyi, Daniel
    Maastricht Univ Med Ctr, Netherlands; Maastricht Univ, Netherlands.
    Knight, Rob
    Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA.
    Laakso, Markku
    Univ Eastern Finland, Finland.
    Laudes, Matthias
    Univ Hosp Schleswig Holstein, Germany.
    Launer, Lenore J.
    NIA, MD 20892 USA.
    Lieb, Wolfgang
    Univ Kiel, Germany.
    Lusis, Aldons J.
    Univ Calif Los Angeles, CA 90024 USA; Univ Calif Los Angeles, CA USA; Univ Calif Los Angeles, CA 90024 USA.
    Masclee, Ad A. M.
    Maastricht Univ Med Ctr, Netherlands; Maastricht Univ, Netherlands.
    Moll, Henriette A.
    Erasmus MC Univ Med Ctr, Netherlands.
    Mujagic, Zlatan
    Maastricht Univ Med Ctr, Netherlands; Maastricht Univ, Netherlands.
    Qibin, Qi
    Albert Einstein Coll Med, NY 10467 USA.
    Rothschild, Daphna
    Weizmann Inst Sci, Israel.
    Shin, Hocheol
    Sungkyunkwan Univ, South Korea; Sungkyunkwan Univ, South Korea.
    Sorensen, Soren J.
    Univ Copenhagen, Denmark.
    Steves, Claire J.
    Kings Coll London, England.
    Thorsen, Jonathan
    Copenhagen Univ Hosp, Denmark.
    Timpson, Nicholas J.
    Univ Bristol, England; Univ Bristol Sch Med, England.
    Tito, Raul Y.
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Vieira-Silva, Sara
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Volker, Uwe
    Univ Med Greifswald, Germany.
    Volzke, Henry
    Univ Med Greifswald, Germany.
    Vosa, Urmo
    Univ Groningen, Netherlands.
    Wade, Kaitlin H.
    Univ Bristol, England; Univ Bristol Sch Med, England.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Watanabe, Kyoko
    Vrije Univ Amsterdam, Netherlands.
    Weiss, Stefan
    Univ Med Greifswald, Germany.
    Weiss, Frank U.
    Univ Med Greifswald, Germany.
    Weissbrod, Omer
    Harvard Univ, MA 02115 USA.
    Westra, Harm-Jan
    Univ Groningen, Netherlands.
    Willemsen, Gonneke
    Vrije Univ, Netherlands.
    Payami, Haydeh
    Univ Alabama Birmingham, AL 35294 USA.
    Jonkers, Daisy M. A. E.
    Maastricht Univ Med Ctr, Netherlands; Maastricht Univ, Netherlands.
    Vasquez, Alejandro Arias
    Univ Texas Hlth Sci Ctr Houston, TX USA; Radboudumc, Netherlands; Radboudumc, Netherlands.
    de Geus, Eco J. C.
    Vrije Univ, Netherlands; Amsterdam UMC, Netherlands.
    Meyer, Katie A.
    Univ N Carolina, NC USA; Univ North Carolina Chapel Hill, NC USA.
    Stokholm, Jakob
    Copenhagen Univ Hosp, Denmark.
    Segal, Eran
    Weizmann Inst Sci, Israel.
    Org, Elin
    Univ Tartu, Estonia.
    Wijmenga, Cisca
    Univ Groningen, Netherlands.
    Kim, Hyung-Lae
    Ewha Womans Univ, South Korea.
    Kaplan, Robert C.
    Fred Hutchinson Canc Res Ctr, WA USA.
    Spector, Tim D.
    Kings Coll London, England.
    Uitterlinden, Andre G.
    Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands.
    Rivadeneira, Fernando
    Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    Lerch, Markus M.
    Univ Med Greifswald, Germany.
    Franke, Lude
    Univ Groningen, Netherlands.
    Sanna, Serena
    Univ Groningen, Netherlands; CNR, Italy.
    DAmato, Mauro
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Monash Univ, Australia; Biodonostia Hlth Res Inst, Spain; Basque Sci Fdn, Spain.
    Pedersen, Oluf
    Univ Copenhagen, Denmark.
    Paterson, Andrew D.
    Hosp Sick Children Res Inst, Canada.
    Kraaij, Robert
    Erasmus MC Univ Med Ctr, Netherlands.
    Raes, Jeroen
    Katholieke Univ Leuven, Belgium; VIB, Belgium.
    Zhernakova, Alexandra
    Univ Groningen, Netherlands.
    Large-scale association analyses identify host factors influencing human gut microbiome composition2021In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, no 2, p. 156-165Article in journal (Refereed)
    Abstract [en]

    To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

  • 14.
    Simon, Rozalyn
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ranasinghe, Purnika
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Queens Univ Belfast, North Ireland.
    Barazanji, Nawroz
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Bergman Jungeström, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Xu, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Serrander, Lena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bazylinski, Dennis A.
    Univ Nevada, NV 89154 USA.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Magnetotactic bacteria from the human gut microbiome associated with orientation and navigation regions of the brain2021In: Journal of Oceanology and Limnology, ISSN 2096-5508, Vol. 39, no 6, p. 2044-2052Article in journal (Refereed)
    Abstract [en]

    Magnetotactic bacteria (MTB), ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals. MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields. Similar magnetite deposits have been found throughout the tissues of the human brain, including brain regions associated with orientation such as the cerebellum and hippocampus, the origins of which remain unknown. Speculation over the role and source of MTB in humans, as well as any association with the brain, remain unanswered. We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions. We identified seven MTB in the human gut microbiome: Magnetococcus marinus, Magnetospira sp. QH-2, Magnetospirillum magneticum, Magnetospirillum sp. ME-1, Magnetospirillum sp. XM-1, Magnetospirillum gryphiswaldense, and Desulfovibrio magneticus. Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus (adjusted for total intracranial volume, uncorrected P<0.05). These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation. These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans. Further studies will be necessary to validate and elucidate the relationship between these bacteria, magnetite concentrations, and brain function.

  • 15.
    Walter, Susanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Sjödahl, Jenny
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Stjernman, Henrik
    Ryhov Hosp Jonkoping, Sweden.
    Hjortswang, Henrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Andreasson, Anna
    Macquarie Univ, Australia; Stockholm Univ, Sweden; Karolinska Inst, Sweden.
    Measuring the impact of gastrointestinal inconvenience and symptoms on perceived health in the general population - validation of the Short Health Scale for gastrointestinal symptoms (SHS-GI)2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 12, p. 1406-1413Article in journal (Refereed)
    Abstract [en]

    Objectives Gastrointestinal (GI) symptoms are intimately related to our wellbeing. The Short Health Scale for GI symptoms (SHS-GI) is a simple questionnaire to measure the impact of GI inconvenience and symptoms on quality of life. The aim was to validate the SHS-GI in a general population sample and to compare it with SHS-data across different patient groups. Method A subsample of 170 participants from a population-based colonoscopy study completed the Rome II questionnaire, GI diaries, psychological questionnaire (hospital anxiety and depression scale) and SHS-GI at follow-up investigation. Psychometric properties of SHS-GI as an overall score were determined by performing a confirmatory factor analysis (CFA). Spearman correlation between SHS total score and symptoms was calculated in the general population sample. SHS-GI data was compared with SHS data from patients with inflammatory bowel disease (IBD) and fecal incontinence (FI). Results As expected, the general population rated their impact of GI inconvenience on quality of life as better than the patient populations in terms of all aspects of the SHS-GI. The CFA showed a good model fit meeting all fit criteria in the general population. Cronbachs alpha for the total scale was 0.80 in the general population sample and ranged from 0.72 in the FI sample to 0.88 and 0.89 in the IBD samples. Conclusions SHS-GI demonstrated appropriate psychometric properties in a sample of the normal population. We suggest that SHS-GI is a valid simple questionnaire suitable for measuring the impact of GI symptoms and inconvenience on quality of life in both general and patient populations.

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  • 16.
    Simon, Rozalyn
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Barazanji, Nawroz
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Icenhour, Adriane
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Univ Duisburg Essen, Germany.
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hamilton, Paul
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 1406Article in journal (Refereed)
    Abstract [en]

    Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood-brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r=- 0.44, p=0.002) and depression (r=- 0.50, p=0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t((33))=3.1, p(FDR)=0.02) and right lateral orbitofrontal cortex (OFC; t((33))=2.9, p(FDR)=0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r=0.28, p=0.007) and left lateral OFC (r=0.29, p=0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.

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  • 17.
    Mathus-Vliegen, Elisabeth
    et al.
    Univ Amsterdam, Netherlands.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ericson, Ann-Charlott
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Weight loss with or without intragastric balloon causes divergent effects on ghrelin cell expression2021In: Obesity Science & Practice, E-ISSN 2055-2238, Vol. 7, no 2, p. 199-207Article in journal (Refereed)
    Abstract [en]

    Objective: The mechanism of action of intragastric balloons in the treatment of obesity is not fully understood. One of the hypotheses is that balloons might have an effect on the fundus, the area of ghrelin production. Methods: Participants were randomized to a 13-week period of sham or balloon treatment followed by a 13-week period of balloon therapy in everyone. Blood samples for ghrelin levels were taken in the fasting state and after a breakfast at the start, after 13 and 26 weeks. Biopsies for ghrelin cell immunohistochemistry were taken from the fundus at endoscopy. Results: Seven participants entered the balloon-balloon (BB) group and 11 the sham-balloon (SB) group. Despite a considerable weight loss, a median -17.9 kg (interquartile ranges -23.8 to -0.5) in the BB group and -18.3 kg (-22.7 to -14.7) in the SB group, fasting ghrelin and meal-induced ghrelin response did not change. In the SB group, the number of ghrelin cells increased significantly (p 0.001) from 110.6 (83.6-118.9) to 160.2 (128.5-223.0) while on sham treatment and returned to initial levels, 116.3 (91.7-146.9) (p 0.001), when they received their first balloon. No significant changes in ghrelin cell numbers were observed in the BB group. Conclusion: In participants without a balloon, weight loss induced an increase in ghrelin cell numbers in the fundus, which was annulled by the subsequent placement of a balloon. The effect of a balloon might be explained by effects on ghrelin cell numbers or ghrelin cell activity.

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  • 18.
    Katinios, Georgios
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Casado-Bedmar, Maite
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Vicario, Maria
    Univ Autonoma Barcelona, Spain.
    Gonzalez-Castro, Ana M.
    Univ Autonoma Barcelona, Spain.
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hjortswang, Henrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared With Irritable Bowel Syndrome and Health2020In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 26, no 7, p. 974-984Article in journal (Refereed)
    Abstract [en]

    Background

    Barrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs).

    Methods

    Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA.

    Results

    Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P < 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P < 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P < 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P < 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P < 0.0005).

    Conclusions

    Results indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.

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  • 19.
    Jönsson, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Bergström, Albin
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Forsell, Camilla
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Simon, Rozalyn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Hotz, Ingrid
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    VisualNeuro: A Hypothesis Formation and Reasoning Application for Multi-Variate Brain Cohort Study Data2020In: Computer graphics forum (Print), ISSN 0167-7055, E-ISSN 1467-8659, Vol. 39, no 6, p. 392-407Article in journal (Refereed)
    Abstract [en]

    We present an application, and its development process, for interactive visual analysis of brain imaging data and clinical measurements. The application targets neuroscientists interested in understanding the correlations between active brain regions and physiological or psychological factors. The application has been developed in a participatory design process and has subsequently been released as the free software VisualNeuro. From initial observations of the neuroscientists workflow, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration requiring the use of many tools side by side. Consequently, our application has been designed to simplify the workflow combining statistical analysis with interactive visual exploration. The resulting environment comprises parallel coordinates for effective overview and selection, Welchs t-test to filter out brain regions with statistically significant differences and multiple visualizations for comparison between brain regions and clinical parameters. These exploration concepts enable neuroscientists to interactively explore the complex bidirectional interplay between clinical and brain measurements and easily compare different patient groups. A qualitative user study has been performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights and is an effective tool for hypothesis formation.

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  • 20.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elsenbruch, Sigrid
    Univ Duisburg Essen, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 13590Article in journal (Refereed)
    Abstract [en]

    Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and gamma-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.

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  • 21.
    Jones, Michael P.
    et al.
    Macquarie Univ, Australia.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Division of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Sweden.
    Kjellstrom, Lars
    Department of Clinical Neuroscience, Sweden.
    Viktorsson, Lisa
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Operations management Region Östergötland, Research and Development Unit. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Talley, Nicholas J.
    Univ Newcastle, Australia.
    Agreus, Lars
    Karolinska Institutet, Sweden.
    Andreasson, Anna
    Karolinska Institutet, Sweden; Stockholm Univ, Sweden.
    Gastrointestinal recall questionnaires compare poorly with prospective patient diaries for gastrointestinal symptoms: data from population and primary health centre samples2019In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 31, no 2, p. 163-169Article in journal (Refereed)
    Abstract [en]

    Background Clinical understanding of gastrointestinal symptoms is commonly based on patient reports of symptom experience. For diagnosis and treatment choices to be appropriate, symptom reports need to be accurate. We examined the agreement between questionnaire recall and prospective diary enumeration of symptoms relevant to the irritable bowel syndrome.

    Patients and methods Data are reported from a randomly selected general population sample (n=238) and also a primary healthcare centre (PHC) sample (n=503, 10 PHCs). All the patients completed the questionnaires, which included Rome III-qualifying irritable bowel syndrome items and a stool and symptom diary over either 7 or 14 days. Agreement between retrospective questionnaire reports and prospective diaries was evaluated.

    Results Concordance between questionnaires and diaries was highest for the simple construct of the occurrence of abdominal pain, although after adjusting for possible chance, agreement was only moderate in the general population sample. More complex constructs, such as pain relieved by defecation, yielded poorer concordance. In general, concordance was stronger among PHC respondents than in the general population sample.

    Conclusion Concordance between questionnaires and diaries was generally poor and related to the complexity of the symptom construct and the type of respondent. The information used to classify individuals based on patient self-report may be unreliable, and therefore, more effort is needed to develop data collection instruments.

  • 22.
    Olsen Faresjö, Åshild
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Norlin, Anna-Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen, Linköping.
    Faresjö, Tomas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Gastrointestinal symptoms - an illness burden that affects daily work in patients with IBS2019In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

    BackgroundIrritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterised by recurrent abdominal pain and disturbed bowel habits and unclear aetiology. IBS is also associated with psychosocial factors, impaired quality of life and lost work productivity. This study sought to determine whether the association between IBS and lost work productivity might be accounted for by poor coping strategies and loss of confidence in the healthcare system.MethodsCase-control design was employed sampling IBS and non-gastrointestinal (non-GI) primary healthcare seekers in a defined region in Sweden. Non-GI patients were of similar age and sex distribution to the IBS patients. Questionnaires applied in this study included instruments designed to measure confidence in the social security system and in the community, as well as questions about whether gastrointestinal problems might affect working life and Sense of coherence (SOC) questionnaire. The studys primary hypothesis was evaluated via an a priori path model.ResultsStatistically significant differences were found between IBS cases (n=305) and controls (n=369) concerning abdominal pain or discomfort affecting everyday performance at work (pamp;lt;0.0001). IBS cases also showed significantly lower (p=0.001) confidence in public healthcare. The studys hypothesis was supported with the finding of a statistically significant indirect association via poor coping strategies, although the indirect associations were lesser in magnitude than the direct association.ConclusionsThis study found a clear association between clinically diagnosed IBS status and interference in work by gastrointestinal symptoms in which sense of coherence might be of importance.

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  • 23.
    Witt, Suzanne Tyson
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jones, Michael P.
    Department of Psychology, Macquarie University, NSW, Australia.
    Elsenbruch, Sigrid
    Institute of Medical Psychology & Behavioral Immunobiology, Essen University Hospital, Essen, Germany.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Mayer, Emeran A.
    Department of Medicine, UCLA, Los Angeles, CA, United States of America.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome2019In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed)
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

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  • 24.
    Simon, Rozalyn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Icenhour, Adriane
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Duisburg Essen, Germany.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Business support and Development, Department of Health and Care Development.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Tillisch, Kirsten
    Univ Calif Los Angeles, CA 90024 USA.
    Mayer, Emeran
    Univ Calif Los Angeles, CA 90024 USA.
    Elsenbruch, Sigrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Duisburg Essen, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    On Functional Connectivity and Symptom Relief After Gut-directed Hypnotherapy in Irritable Bowel Syndrome: A Preliminary Study2019In: JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY, ISSN 2093-0879, Vol. 25, no 3, p. 478-479Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 25.
    Norlin, Anna-Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen, Linköping.
    Olsen Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kärna, Linköping.
    Jones, Michael P.
    Macquarie Univ, Australia.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Primary healthcare utilisation and self-rated health among patients with Irritable Bowel Syndrome: What are the impacts of comorbidities, gastrointestinal symptom burden, sense of coherence and stress?2019In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 119Article in journal (Refereed)
    Abstract [en]

    Objectives: Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disease associated with impaired quality of life and an increased use of healthcare services. Self-ratings of health have proven a powerful predictor of health outcomes. The aim of this study was to evaluate the unique impacts of comorbidities, gastrointestinal symptoms, perceived stress and sense of coherence on the number of healthcare contacts and self-rated health of IBS patients in Swedish primary care. Methods: In this cross-sectional study, 186 primary-care IBS patients and 360 non-IBS patients (as a reference group) were administrated a test battery of validated questionnaires. Data on comorbidities and healthcare-seeking frequency were obtained from a registry. Results: In the reduced multivariable logistic regression model, average days of abdominal pain/week (OR = 0.83, 95% CI = 0.72-0.96), age (OR = 0.95, 95% CI = 0.92-0.97) and sense of coherence (OR = 1.07, 95% CI = 1.03-1.11) remained independent, statistically significant predictors of IBS (and non-IBS) patients reporting good health. Only the number of comorbidities in general (OR = 1.22, 95% CI = 1.14-1.32) and sleep disorders in particular (OR = 5.40, 95% CI = 1.85-15.76) independently predicted high levels of primary healthcare utilisation among IBS patients. Conclusion: Lack of gastrointestinal symptoms, a high sense of coherence and younger age were associated with better self-rated health in both IBS and non-IBS patients. The number of comorbidities in general and sleep disorders in particular were associated with frequent PHC contacts in IBS patients. The association between frequent primary-care contacts and sleep disorders was not seen in the control group, indicating a unique association with IBS patients.

  • 26.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Icenhour, Adriane
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Elsenbruch, Sigrid
    Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome2019In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

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    Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
  • 27.
    Jönsson, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Bergström, Albin
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Algström, Isac
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Simon, Rozalyn
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hotz, Ingrid
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Visual analysis for understanding irritable bowel syndrome2019In: Biomedical visualisation / [ed] Paul Rea, Cham: Springer, 2019, p. 111-122Chapter in book (Refereed)
    Abstract [en]

    The cause of irritable bowel syndrome (IBS), a chronic disorder characterized by abdominal pain and disturbed bowel habits, is largely unknown. It is believed to be related to physical properties in the gut, central mechanisms in the brain, psychological factors, or a combination of these. To understand the relationships within the gut-brain axis with respect to IBS, large numbers of measurements ranging from stool samples to functional magnetic resonance imaging are collected from patients with IBS and healthy controls. As such, IBS is a typical example in medical research where research turns into a big data analysis challenge. In this chapter we demonstrate the power of interactive visual data analysis and exploration to generate an environment for scientific reasoning and hypothesis formulation for data from multiple sources with different character. Three case studies are presented to show the utility of the presented work.

  • 28.
    Hadizadeh, Fatemeh
    et al.
    Karolinska Inst, Sweden; Isfahan Univ Med Sci, Iran.
    Bonfiglio, Ferdinando
    Karolinska Inst, Sweden; BioDonostia Hlth Res Inst, Spain.
    Belheouane, Meriem
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Vallier, Marie
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Sauer, Sascha
    Max Delbruck Ctr Mol Med BIMSB BIH, Germany.
    Bang, Corinna
    Christian Albrechts Univ Kiel, Germany.
    Bujanda, Luis
    BioDonostia Hlth Res Inst, Spain; Univ Pais Vasco UPV EHU, Spain.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Engstrand, Lars
    Karolinska Inst, Sweden; Sci Life Lab, Sweden.
    Talley, Nicholas J.
    Karolinska Inst, Sweden; Univ Newcastle, Australia; Mayo Clin, MN USA; AGIRA, Australia.
    Rafter, Joseph
    Karolinska Inst, Sweden.
    Baines, John F.
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    BioDonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Faecal microbiota composition associates with abdominal pain in the general population2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 4, p. 778-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 29.
    Bonfiglio, Ferdinando
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Garcia-Etxebarria, Koldo
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Bresso, Francesca
    Karolinska Univ Hosp, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Karolinska Inst, Sweden.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Nardone, Gerardo
    Univ Federico II, Italy.
    Cuomo, Rosario
    Federico II Univ Hosp, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova Univ Hosp, Italy.
    Neri, Matteo
    G DAnnunzio Univ and Fdn, Italy; G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    Univ Bari, Italy.
    Bellini, Massimo
    Univ Pisa, Italy.
    Barbara, Giovanni
    Univ Bologna, Italy.
    Latiano, Anna
    Casa Sollievo Sofferenza Hosp, Italy.
    Huebenthal, Matthias
    Christian Albrechts Univ Kiel, Germany.
    Thijs, Vincent
    Florey Inst Neurosci and Mental Hlth, Australia.
    Netea, Mihai G.
    Radboud Univ Nijmegen, Netherlands; Radboud Univ Nijmegen, Netherlands; Univ Bonn, Germany.
    Jonkers, Daisy
    Maastricht Univ, Netherlands.
    Chang, Lin
    Univ Calif Los Angeles, CA 90095 USA.
    Mayer, Emeran A.
    Univ Calif Los Angeles, CA 90095 USA.
    Wouters, Mira M.
    Katholieke Univ Leuven, Belgium.
    Boeckxstaens, Guy
    Katholieke Univ Leuven, Belgium.
    Camilleri, Michael
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    Zhernakova, Alexandra
    Univ Med Ctr Groningen, Netherlands.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Ikerbasque, Spain.
    Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome2018In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, no 1, p. 168-179Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctors diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P amp;lt; 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also [GRAPHICS] associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

  • 30.
    Henström, Maria
    et al.
    Karolinska Institute, Sweden.
    Diekmann, Lena
    University of Vet Medical Hannover, Germany.
    Bonfiglio, Ferdinando
    Karolinska Institute, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden.
    Kuech, Eva-Maria
    University of Vet Medical Hannover, Germany.
    von Koeckritz-Blickwede, Maren
    University of Vet Medical Hannover, Germany.
    Thingholm, Louise B.
    Christian Albrechts University of Kiel, Germany.
    Zheng, Tenghao
    Karolinska Institute, Sweden.
    Assadi, Ghazaleh
    Karolinska Institute, Sweden.
    Dierks, Claudia
    University of Vet Medical Hannover, Germany.
    Heine, Martin
    University of Vet Medical Hannover, Germany.
    Philipp, Ute
    University of Vet Medical Hannover, Germany.
    Distl, Ottmar
    University of Vet Medical Hannover, Germany.
    Money, Mary E.
    University of Maryland, MD 21201 USA; Meritus Medical Centre, MD USA.
    Belheouane, Meriem
    Max Planck Institute Evolutionary Biol, Germany; Christian Albrechts University of Kiel, Germany.
    Heinsen, Femke-Anouska
    Christian Albrechts University of Kiel, Germany.
    Rafter, Joseph
    Karolinska Institute, Sweden.
    Nardone, Gerardo
    Federico II University Hospital, Italy.
    Cuomo, Rosario
    Federico II University Hospital, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova University Hospital, Italy.
    Neri, Matteo
    GDAnnunzio University, Italy; University of GDAnnunzio, Italy.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Simren, Magnus
    University of Gothenburg, Sweden; University of N Carolina, NC USA.
    Karling, Pontus
    Umeå University, Sweden.
    Ohlsson, Bodil
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Schmidt, Peter T.
    Karolinska University Hospital, Sweden.
    Lindberg, Greger
    Karolinska University Hospital, Sweden.
    Dlugosz, Aldona
    Karolinska University Hospital, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Mayer, Emeran
    University of Calif Los Angeles, CA USA.
    Baines, John F.
    Max Planck Institute Evolutionary Biol, Germany; Christian Albrechts University of Kiel, Germany.
    Engstrand, Lars
    Karolinska Institute, Sweden.
    Portincasa, Piero
    University of Bari Aldo Moro, Italy.
    Bellini, Massimo
    University of Pisa, Italy.
    Stanghellini, Vincenzo
    University of Bologna, Italy.
    Barbara, Giovanni
    University of Bologna, Italy.
    Chang, Lin
    University of Calif Los Angeles, CA USA.
    Camilleri, Michael
    Mayo Clin, MN USA.
    Franke, Andre
    Christian Albrechts University of Kiel, Germany.
    Naim, Hassan Y.
    University of Vet Medical Hannover, Germany.
    DAmato, Mauro
    Karolinska Institute, Sweden; BioDonostia Health Research Institute, Spain; Basque Science Fdn, Spain; Karolinska Institute, Sweden.
    Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (pamp;lt;0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

  • 31.
    Garcia-Etxebarria, Koldo
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Bonfiglio, Ferdinando
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Univ Basque Country, Spain.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Nardone, Gerardo
    University Federico II, Naples, Italy.
    Cuomo, Rosario
    Federico II Univ Hosp, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova Univ Hosp, Italy.
    Neri, Matteo
    G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    G DAnnunzio Univ and Fdn, Italy.
    Bellini, Massimo
    Univ Bari, Italy.
    Barbara, Giovanni
    Univ Pisa, Italy.
    Jonkers, Daisy
    Univ Bologna, Italy.
    Eswaran, Shanti
    Univ Michigan, MI USA.
    Chey, William D.
    Univ Michigan, MI USA.
    Kashyap, Purna
    Mayo Clin, MN USA.
    Chang, Lin
    Univ Calif Los Angeles, CA 90095 USA.
    Mayer, Emeran A.
    Univ Calif Los Angeles, CA 90095 USA.
    Wouters, Mira M.
    Katholieke Univ Leuven, Belgium.
    Boeckxstaens, Guy
    Katholieke Univ Leuven, Belgium.
    Camilleri, Michael
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Franke, Andre
    Maastricht Univ, Netherlands; Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients2018In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 16, no 10, p. 1673-1676Article in journal (Other academic)
    Abstract [en]

    n/a

    Download full text (pdf)
    fulltext
  • 32.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elsenbruch, Sigrid
    University of Duisburg Essen, Germany.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tillisch, Kirsten
    University of Calif Los Angeles, CA USA.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA USA.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome2017In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 15, p. 449-457Article in journal (Refereed)
    Abstract [en]

    Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N= 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.

  • 33.
    Norlin, Anna-Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Tegelstrom, V
    National board of forensic medicine, Sweden.
    Grodzinsky, Ewa
    Linköping University, Department of Social and Welfare Studies. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Jones, M P
    Psychology Department, Macquarie University, Sydney, NSW, Australia..
    Faresjö, Åshild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cortisol levels in hair are altered in irritable bowel syndrome - A case control study in primary care.2017In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 93, p. 69-75, article id S0022-3999(16)30613-4Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls.

    METHODS: In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints. The participants donated hair samples and completed questionnaires including a scale of self-reported perceived stress (PSS). 169 Rome III-fulfilling IBS patients and 316 non-IBS patients were available for final analyses.

    RESULTS: IBS patients had significantly lower HCC, median=16.3pg/mg, IQR=26.9pg/mg, compared to non-IBS patients, median=22.8pg/mg, IQR=29.1pg/mg. There was also a difference in the distribution of HCC quintiles between the two groups, with 30.2% IBS patients and 14.2% of non-IBS patients in the lowest quintile of HCC. PSS was higher among IBS patients with a mean (SD) total score of 25.3 (8.0) compared to controls 21.4, (7.5). Quintiles of HCC and PSS stayed significantly but very weakly related to IBS (B=-0.332, Std error=0.146, p<0.005) in multivariable analyses.

    CONCLUSION: This study suggests a possible suppression of the HPA-axis activity in a considerable portion of IBS patients.

  • 34.
    Jankipersadsing, Soesma A.
    et al.
    University of Groningen, Netherlands; University of Groningen, Netherlands.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden; Isfahan University of Medical Science, Iran.
    Jan Bonder, Marc
    University of Groningen, Netherlands.
    Tigchelaar, Ettje F.
    University of Groningen, Netherlands; Top Institute Food and Nutr, Netherlands.
    Deelen, Patrick
    University of Groningen, Netherlands.
    Fu, Jingyuan
    University of Groningen, Netherlands.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Wijmenga, Cisca
    University of Groningen, Netherlands.
    Hysi, Pirro
    Kings Coll London, England.
    DAmato, Mauro
    Karolinska Institute, Sweden; BioDonostia Health Research Institute San Sebastian, Spain; Basque Fdn Science, Spain.
    Zhernakova, Alexandra
    University of Groningen, Netherlands.
    Letter: A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency in GUT, vol 66, issue 4, pp 756-7582017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 4, p. 756-758Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 35.
    Hadizadeh, Fatemeh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; School of Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Belheouane, Meriem
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Heinsen, Femke-Anouska
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    Andreasson, Anna
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Agreus, Lars
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Clinical Genomics Facility, Science for Life Laboratory, Stockholm, Sweden.
    Baines, John F
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Rafter, Joseph
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Franke, Andre
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    DAmato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Stool frequency is associated with gut microbiota composition2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 3, p. 559-560Article in journal (Other academic)
  • 36.
    Henström, Maria
    et al.
    Karolinska Institute, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Institute, Sweden; Isfahan University of Medical Science, Iran.
    Beyder, Arthur
    Mayo Clin, MN USA.
    Bonfiglio, Ferdinando
    Karolinska Institute, Sweden; BioDonostia Health Research Institute, Spain.
    Zheng, Tenghao
    Karolinska Institute, Sweden.
    Assadi, Ghazaleh
    Karolinska Institute, Sweden.
    Rafter, Joseph
    Karolinska Institute, Sweden.
    Bujanda, Luis
    BioDonostia Health Research Institute, Spain.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stockholm University, Sweden.
    Dlugosz, Aldona
    Karolinska Institute, Sweden.
    Lindberg, Greger
    Karolinska Institute, Sweden.
    Schmidt, Peter T.
    Karolinska Institute, Sweden.
    Karling, Pontus
    Umeå University, Sweden.
    Ohlsson, Bodil
    Lund University, Sweden.
    Talley, Nicholas J.
    University of Newcastle, Australia.
    Simren, Magnus
    University of Gothenburg, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Wouters, Mira
    Leuven University, Belgium.
    Farrugia, Gianrico
    Mayo Clin, MN USA.
    DAmato, Mauro
    BioDonostia Health Research Institute, Spain; BioCruces Health Research Institute, Spain; Basque Fdn Science, Spain; Karolinska Institute, Sweden.
    TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 9, p. 1725-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 37.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Salvo-Romero, Eloisa
    University of Autonoma Barcelona, Spain.
    Vicario, Maria
    University of Autonoma Barcelona, Spain.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA 90095 USA.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, p. 948-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.

  • 38.
    Lundberg, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Bednarska, O.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Witt, ST
    Elsenbruch, S
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Increased inhibitory neurotransmission within anterior cingulate cortex is related to comorbid anxiety in irritable bowel syndrome.2016Conference paper (Other academic)
  • 39.
    Walter, Susanna A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lundengård, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Simon, Rozalyn
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Torkildsen Nilsson, Maritha
    The National Board of Forensic Medicine and Linköping University, Linköping, Sweden.
    Söderfeldt, Birgitta
    Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 3Article in journal (Refereed)
    Abstract [en]

    Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.

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  • 40.
    Sjödahl, Jenny
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Johansson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ingemansson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ryn, Ann-Katrine
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Combination therapy with biofeedback, loperamide, and stool-bulking agents is effective for the treatment of fecal incontinence in women - a randomized controlled trial2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 8, p. 965-974Article in journal (Refereed)
    Abstract [en]

    Objective. Biofeedback and medical treatments have been extensively used for moderate fecal incontinence (FI). There is limited data comparing and combining these two treatments. The objective of this study was to evaluate the effect of biofeedback and medical treatments, separately and in combination. Material and methods. Sixty-four consecutive female patients, referred to a tertiary centre for FI, were included. The patients were randomized to start with either biofeedback (4-6 months) or medical treatment with loperamide and stool-bulking agents (2 months). Both groups continued with a combination of treatments, i.e. medical treatment was added to biofeedback and vice versa. A two-week prospective bowel symptom diary and anorectal physiology were evaluated at baseline, after single-and combination treatments. Results. Fifty-seven patients completed the study. Median number of leakage episodes during two weeks decreased from 6 to 3 (p less than 0.0001) from baseline to completion. The patients showed a significant (1) decrease in number of leakages without forewarning (p = 0.04); (2) decrease in number of stools with urgency (p = 0.001); (3) decrease in number of loose stool consistency; and (4) an increase in rectal sensory thresholds, both for maximum tolerable rectal pressure and first sensation (less than 0.01). The combination treatment was superior to both single treatments in terms of symptoms and functions. There was no significant difference between the two groups at any time point. Conclusions. The combination therapy with biofeedback and medical treatment is effective for symptom relief in FI. The symptom improvement was associated with improved fecal consistency, reduced urgency, and increased rectal sensory thresholds.

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  • 41.
    Lowén, Mats B. O.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mayer, E.
    Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
    Tillisch, K.
    Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
    Labus, J.
    Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
    Naliboff, B.
    Oppenheimer Center for Neurobiology of Stress, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Thorell, Lars-Håkan
    Emotra AB, Gothenburg, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity2015In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 5, p. 646-655Article in journal (Refereed)
    Abstract [en]

    Background Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.

    Methods Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.

    Key Results While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.

    Conclusions & Inferences These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.

  • 42.
    Ek, Weronica E
    et al.
    Karolinska Institutet, Stockholm .
    Reznichenko, Anna
    Karolinska Institutet, Stockholm.
    Ripke, Stephan
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Niesler, Beate
    University of Heidelberg, Germany .
    Zucchelli, Marco
    Karolinska Institutet, Stockholm.
    Rivera, Natalia V
    Karolinska Institutet, Stockholm.
    Schmidt, Peter T
    University Hospital, Karolinska institutet, Stockholm .
    Pedersen, Nancy L
    Karolinska Institutet, Stockholm.
    Magnusson, Patrik
    Karolinska Institutet, Stockholm.
    Talley, Nicholas J
    University of Newcastle, Australia .
    Holliday, Elizabeth G
    University of Newcastle, Australia .
    Houghton, Lesley
    University of Manchester UK and Mayo Clinic, Jacksonville USA.
    Gazouli, Maria
    University of Athens, Greece .
    Karamanolis, George
    University of Athens, Greece .
    Rappold, Gudrun
    University of Heidelberg, Germany.
    Burwinkel, Barbara
    University Women's Clinic, University of Heidelberg, Germany.
    Surowy, Harald
    University Women's Clinic, University of Heidelberg, Germany.
    Rafter, Joseph
    Karolinska Institutet, Stockholm .
    Assadi, Ghazaleh
    Karolinska Institutet, Stockholm .
    Li, Ling
    Karolinska Institutet, Stockholm .
    Papadaki, Evangelia
    Karolinska Institutet, Stockholm .
    Gambaccini, Dario
    University of Pisa, Pisa Italy .
    Marchi, Santino
    University of Pisa, Pisa Italy .
    Colucci, Rocchina
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Blandizzi, Corrado
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Barbaro, Raffaella
    University of Bologna, Italy .
    Karling, Pontus
    Umeå University .
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ohlsson, Bodil
    Skånes University Hospital, Malmö .
    Tornblom, Hans
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Bresso, Francesca
    Karolinska University Hospital, Stockholm .
    Andreasson, Anna
    Sweden Stress Research Institute, Stockholm University.
    Dlugosz, Aldona
    Karolinska Instituet, Stockholm .
    Simren, Magnus
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Agreus, Lars
    Karolinska Institutet Stockholm .
    Lindberg, Greger
    Karolinska University Hospital, Karolinska Institutet, Stockholm.
    Boeckxstaens, Guy
    Leuven University, Leuven, Belgium .
    Bellini, Massimo
    University of Pisa, Italy .
    Stanghellini, Vincenzo
    University of Bologna, Italy .
    Barbara, Giovanni
    University of Bologna, Italy .
    Daly, Mark J
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Camilleri, Michael
    Mayo Clinic, Rochester, Minnesota, USA .
    Wouters, Mira M
    Leuven University, Belgium .
    D'Amato, Mauro
    Karolinska Institutet, Stockholm .
    Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, p. 1774-1782Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies.

    DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls.

    RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls.

    CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

  • 43.
    Molinder, Herdis
    et al.
    Karolinska Institute, Sweden.
    Agreus, Lars
    Karolinska Institute, Sweden.
    Kjellström, Lars
    Sabbatsberg Hospital, Sweden.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Talley, Nicholas J.
    University of Newcastle, Australia.
    Andreasson, Anna
    Karolinska Institute, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Nyhlin, Henry
    Karolinska Institute, Sweden.
    How individuals with the irritable bowel syndrome describe their own symptoms before formal diagnosis2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 276-279Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate how individuals fulfilling the Rome II criteria for irritable bowel syndrome (IBS) spontaneously described their symptoms. Method: From a general population, 1,244 randomly sampled adults were asked to describe their gastrointestinal symptoms (if any) verbally, in their own words, at a semi-structured interview. Their own descriptions were sorted into five symptom clusters. The participants independently completed a written questionnaire (the Rome II Modular Questionnaire (RMIIMQ)). Results: A total of 601 participants reported at least one gastrointestinal symptom, and 128 had IBS according to the RMIIMQ. After exclusion of organic causes, previously diagnosed IBS, or additional gastrointestinal diagnosis, 81 participants with IBS according to RMIIMQ remained. Five participants (6%) described symptoms included in the full definition of IBS, but none fulfilled the Rome II criteria completely. Abdominal pain or other IBS-related symptoms were reported by 64 (79%), and 12 (15%) did not report any IBS-like symptom. Conclusion: Previously undiagnosed individuals, who fulfil criteria for Rome II-IBS, often express their complaints in words that do not fit into the current diagnostic criteria.

  • 44.
    Grodzinsky, Ewa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Viktorsson, Lisa
    Carlsson, Ann-Kristin
    Jones, Michael P.
    Macquarie University, Australia.
    Olsen Faresjö, Ashild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS - a case-control study in primary care2015In: BMC Family Practice, E-ISSN 1471-2296, Vol. 16, no 6Article in journal (Refereed)
    Abstract [en]

    Background

    Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder,that affects approximately 10% of the general population and the majority are diagnosed  in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to  investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care.     

    Methods

    A case–control study in primary care setting among IBS patients meeting the ROME III         criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any         present or previous gastrointestinal complaints. The data were collected through self-reportedquestionnaires of psychosocial factors.     

    Results

    IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores         for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report ‘good’ health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation  in negative self-esteem among IBS patients remained statistically significant (p =0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04).     

    Conclusions

    The more frequently reported negative self-esteem and inferior coping strategies among         IBS patients found in this study suggest the possibility that psychological therapies         might be helpful for these patients. However these data do not indicate the causal         direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

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  • 45.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Neurotransmittor Concentration in Pregenual ACC in Stool Consistency Patient Subgroups With IBS2014Conference paper (Refereed)
    Abstract [en]

    Introduction

    The Anterior Cingulate Cortex (ACC) is a key region of the central autonomic brain network. Irritable Bowel Syndrome (IBS) is characterized abdominal pain and bowel habit disturbances. Autonomic dysregulation has been reported in IBS as well as altered ACC activation in pregenual ACC during visceral stimulation 1 2. Glutamate is the major excitatory and Gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain.

    Aim & Methods

    We aimed to measure neurotransmitter concentration in the pregenual ACC, in stool consistency subgroups with IBS by using quantitative neurotransmitter Magnetic Resonance Spectroscopy (qMRS)Seven patients with IBS-mixed (6 women) and five patients with IBS -diarrhea (4 women) according to Rome 3 were included. Mean age was 34.2 years (SD 5.3) with no significant difference between subgroups.  Patients completed symptom severity score (IBS-SSS). Quantitative MRS was measured in a 3T MRI scanner. A water-suppressed MEGA-PRESS sequence (TR 2.0 s, TE 68 ms) was used with the editing pulses placed at 1.90 ppm (‘ON-dynamics’) and at 7.46 ppm (‘OFF-dynamics’) with a voxel (3x3x3 cm3) placed in the pACC. Each MEGA-PRESS measurement resulted in a sequence of 40 OFF- and ON-dynamics, where each was computed by 8 phase cycles. Directly after each water-suppressed MEGA-PRESS measurement, a shorter 2-dynamic unsuppressed water MEGA-PRESS measurement was performed within the same voxel, which was used to obtain the concentrations in physically well-defined units of [mM]. The GABA concentrations were computed by averaging the difference spectra obtained by subtracting each OFF-dynamic from subsequent ON-dynamic and using LCModel (Version 6.3) for the final quantification. The Glutamate concentrations were obtained by only averaging the OFF-dynamics, which were not affected by the editing pulses. Additionally, all dynamics were phase and frequency corrected prior to the averaging. For group comparison unpaired T-tests were used.

    Results

    Patients had moderate to severe symptoms with IBS-SSS of 367 (SD 79.7). There was no significant difference between IBS subgroups in terms of IBS-SSS. Mean pACC GABA concentration was 1.66 (SD 0.17) mM in IBS-M and 1.65 (SD 0.27) mM in IBS-D. There was no significant difference between groups (p=0.9). Mean pACC Glutamate concentration was 4.54 (0.35) mM in IBS-M and 5.13 (SD 0.64) mM in IBS-D. There was no significant difference between groups, although a trend with p=0.06 was observed.

    Conclusion

    Further qMRS data have to be collected in IBS patients as well as healthy controls to evaluate if IBS subgroups demonstrate alterations in pACC glutamate and GABA concentrations

  • 46.
    Walter, Susanna
    et al.