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  • 1.
    Andersen, Vibeke
    et al.
    Medical Department, Sygehus Sønderjylland Aabenraa, Aabenraa, Denmark; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Vogel, Ulla
    National Research Centre for the Working Environment, Copenhagen, Denmark.
    Colorectal cancer in patients with inflammatory bowel disease: can we predict risk?2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 31, p. 4091-4094Article in journal (Refereed)
    Abstract [en]

    The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.

  • 2. Bergquist, Annika
    et al.
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Lund, Ulrika
    Ekbom, Anders
    Olsson, Rolf
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Broomé, Ulrika
    Perinatal events and the risk of developing primary sclerosing cholangitis2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 37, p. 6037-6040Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether perinatal events, intrauterine or postpartum, are associated with the development of primary sclerosing cholangitis (PSC) later in life.

    METHODS: Birth records from 97 patients with adult PSC in Sweden were reviewed. Information on perinatal events including medications and complications during pregnancy, gestation length, birth weight and length were collected. Two control children of the same sex were selected for each subject. Conditional multiple logistic regression was used to assess associations of the perinatal measures with development of PSC.

    RESULTS: No significant associations were found between gestational age, birth length, breastfeeding, and the majority of medical complications including infections or medication during pregnancy for the mothers or postpartum for the children. Vaginal bleeding and peripheral oedema showed associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and 2.28 (95% CI, 1.04-5.03), respectively.

     

    CONCLUSION: The associations of vaginal bleeding and oedema with subsequent PSC cannot readily be explained, so our findings do not strongly support the hypothesis of a significant role of perinatal events as a risk for the development of PSC later in life.

  • 3. Blom, Kristin
    et al.
    Rubin, Jenny
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Intestinal Medicine, Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Rönnblom, Anders
    Sangfelt, Per
    Lördal, Mikael
    Jönsson, Ulla-Britt
    Sjöqvist, Urban
    Håkansson, Lena Douhan
    Venge, Per
    Carlson, Marie
    Eosinophil associated genes in the inflammatory bowel disease 4 region: correlation to inflammatory bowel disease revealed2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 44, p. 6409-6419Article in journal (Refereed)
    Abstract [en]

    AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).

    METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP(®) system as described by the manufacturer. Statistical tests for calculations of results were χ(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.

    RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.

    CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

  • 4.
    Daferera, Niki
    et al.
    Linköping University, Linköping, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ignatova, Simone
    Linköping University, Linköping, Sweden .
    Ström, Magnus
    Linköping University, Linköping, Sweden.
    Münch, Andreas
    Linköping University, Linköping, Sweden.
    Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed)
    Abstract [en]

    In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

  • 5.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences.
    Rademacher, Lech
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Avesta Hospital, Avesta, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis2017In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 23, no 7, p. 1319-1324Article in journal (Refereed)
    Abstract [en]

    One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC.

  • 6.
    Günaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 34, p. 12249-12259Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

  • 7.
    Halfvarson, Jonas
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cummings, Fraser
    Department of Gastroenterology, Southampton University Hospital NHS Foundation Trust, Southampton, Hampshire, United Kingdom.
    Grip, Olof
    Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden.
    Savoye, Guillaume
    Service d'Hépato-Gastroentérologie, CHU de Rouen-Hôpital Charles Nicolle, Rouen, France.
    Inflammatory bowel disease registries for collection of patient iron parameters in Europe2018In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 24, no 10, p. 1063-1071Article, review/survey (Refereed)
    Abstract [en]

    Iron deficiency without anemia and iron deficiency anemia are common and frequently overlooked complications of inflammatory bowel disease. Despite the frequency and impact of iron deficiency in inflammatory bowel disease, there are gaps in our understanding about its incidence, prevalence and natural history and, consequently, patients may be undertreated. Medical registries have a key role in collecting data on the disease's natural history, the safety and effectiveness of drugs in routine clinical practice, and the quality of care delivered by healthcare services. Even though iron deficiency impacts inflammatory bowel disease patients and healthcare systems substantially, none of the established European inflammatory bowel disease registries systematically collects information on iron parameters and related outcomes. Collection of robust iron parameter data from patient registries is one way to heighten awareness about the importance of iron deficiency in this disease and to generate data to improve the quality of patient care, patient outcomes, and thus quality of life. This objective could be achieved through collection of specific laboratory, clinical, and patient-reported measurements that could be incorporated into existing registries. This review describes the status of current European inflammatory bowel disease registries and the data they generate, in order to highlight their potential role in collecting iron data, to discuss how such information gathering could contribute to our understanding of iron deficiency anemia, and to provide practical information in regard to the incorporation of accumulated iron parameter data into registries.

  • 8.
    Halkjær, Sofie Ingdam
    et al.
    Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
    Lo, Bobby
    Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
    Cold, Frederik
    Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
    Højer Christensen, Alice
    Holster, Savanne
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Aroniadis, Olga C.
    Renaissance School of Medicine, Stony Brook University Hospital, New York, NY 11794-8434, United States.
    Lahtinen, Perttu
    Central Hospital, Lahti 15850, Finland; University of Helsinki, Helsinki 00014, Finland.
    Holvoet, Tom
    University Hospital Ghent, Ghent 9000, Belgium.
    Gluud, Lise Lotte
    University of Copenhagen, Copenhagen 2200, Denmark .
    Petersen, Andreas Munk
    Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; University of Copenhagen, Copenhagen 2200, Denmark .
    Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis2023In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 29, no 20, p. 3185-3202Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND; Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients’ quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as ‘gut dysbiosis’. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.

    AIM: To assess the efficacy and safety of FMT for the treatment of IBS.

    METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.

    RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.

    CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed

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  • 9.
    Kajander, Kajsa
    et al.
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Valio Ltd, Research Centre, Helsinki, Finland.
    Myllyluoma, Eveliina
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Valio Ltd, Research Centre, Helsinki, Finland.
    Kyrönpalo, Sinikka
    Tampere Health Centre and Department of Medicine, Tampere City Hospital, Tampere, Finland.
    Rasmussen, Martin
    Tampere Health Centre and Department of Medicine, Tampere City Hospital, Tampere, Finland.
    Sipponen, Pentti
    Department of Pathology, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppänen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Vapaatalo, Heikki
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
    Oresic, Matej
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Korpela, Riitta
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Valio Ltd, Research Centre, Helsinki, Finland.
    Elevated pro-inflammatory and lipotoxic mucosal lipids characterise irritable bowel syndrome2009In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 15, no 48, p. 6068-6074Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the pathophysiology of irritable bowel syndrome (IBS) by comparing the global mucosal metabolic profiles of IBS patients with those of healthy controls.

    METHODS: Fifteen IBS patients fulfilling the Rome II criteria, and nine healthy volunteers were included in the study. A combined lipidomics (UPLC/MS) and metabolomics (GC x GC-TOF) approach was used to achieve global metabolic profiles of mucosal biopsies from the ascending colon.

    RESULTS: Overall, lipid levels were elevated in patients with IBS. The most significant upregulation was seen for pro-inflammatory lysophosphatidylcholines. Other lipid groups that were significantly upregulated in IBS patients were lipotoxic ceramides, glycosphingolipids, and di- and triacylglycerols. Among the metabolites, the cyclic ester 2(3H)-furanone was almost 14-fold upregulated in IBS patients compared to healthy subjects (P = 0.03).

    CONCLUSION: IBS mucosa is characterised by a distinct pro-inflammatory and lipotoxic metabolic profile. Especially, there was an increase in several lipid species such as lysophospholipids and ceramides.

  • 10.
    Kekkonen, Riina-A.
    et al.
    University of Helsinki, Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Valio Ltd, Research Centre, Helsinki, Finland.
    Sysi-Aho, Marko
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppanen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Julkunen, Ilkka
    Department of Viral Diseases and Immunology, Helsinki, Finland.
    Vapaatalo, Heikki
    University of Helsinki, Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
    Oresic, Matej
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Korpela, Riitta
    University of Helsinki, Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Valio Ltd, Research Centre, Helsinki, Finland.
    Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 20, p. 3188-3194Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the effect of three weeks' intervention with a probiotic Lactobacillus rhamnosus GG (LGG) bacteria on global serum lipidomic profiles and evaluate whether the changes in inflammatory variables (CRP, TNF-alpha and IL-6) are reflected in the global lipidomic profiles of healthy adults.

    METHODS: We performed UPLC/MS-based global lipidomic platform analysis of serum samples (n = 26) in a substudy of a randomised, double-blind, placebo-controlled 3-wk clinical intervention trial investigating the immunomodulatory effects of probiotics in healthy adults.

    RESULTS: A total of 407 lipids were identified, corresponding to 13 different lipid classes. Serum samples showed decreases in the levels of lysophosphatidylcholines (LysoGPCho), sphingomyelins (SM) and several glycerophosphatidylcholines (GPCho), while triacylglycerols (TAG) were mainly increased in the probiotic LGG group during the intervention. Among the inflammatory variables, IL-6 was moderately associated by changes in global lipidomic profiles, with the top-ranked lipid associated with IL-6 being the proinflammatory LysoGPCho (20:4). There was a weak association between the lipidomic profiles and the two other inflammatory markers, TNF-alpha and CRP.

    CONCLUSION: This was the first study to investigate the effects of probiotic intervention on global lipidomic profiles in humans. There are indications that probiotic LGG intervention may lead to changes in serum global lipid profiles, as reflected in decreased GPCho, LysoGPCho and SM as well as mainly increased TAG.

  • 11.
    Pilvi, Taru-K.
    et al.
    Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Foundation for Nutrition Research, Helsinki, Finland; Valio Ltd, Research Center, Valio, Helsinki, Finland.
    Seppanen-Laakso, Tuulikki
    VTT Technical Research Centre of Finland, Finland.
    Simolin, Helena
    VTT Technical Research Centre of Finland, Finland.
    Finckenberg, Piet
    Institute of Biomedicine, Pharmacology, Biomedicum Helsink, University of Helsinki, Helsinki, Finland.
    Huotari, Anne
    Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland.
    Herzig, Karl-Heinz
    Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland; Institute of Biomedicine, Department of Physiology, and Biocenter of Oulu, University of Oulu, Oulu, Finland.
    Korpela, Riitta
    Institute of Biomedicine, Pharmacology, Biomedicum Helsink, University of Helsinki, Helsinki, Finland; Foundation for Nutrition Research, Helsinki, Finland; Valio Ltd, Research Center, Valio, Helsinki, Finland.
    Oresic, Matej
    VTT Technical Research Centre of Finland, Finland.
    Mervaala, Eero-M.
    Institute of Biomedicine, Pharmacology, Biomedicum Helsink, University of Helsinki, Helsinki, Finland.
    Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 28, p. 4462-4472Article in journal (Refereed)
    Abstract [en]

    AIM: To characterise the effect of energy restriction (ER) on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium.

    METHODS: Liver metabolomic profile of lean and obese C57Bl/6J mice (n = 10/group) were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet (whey + Ca). The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.

    RESULTS: ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey + Ca diet significantly decreased blood glucose (P < 0.001) and serum insulin (P < 0.01). In hepatic lipid species the biggest reduction was in the level of triacylglycerols and ceramides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey + Ca ER group (P < 0.001, vs obese). ER on whey + Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic ceramides (P < 0.001, vs obese; P > 0.05, vs lean). These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway metabolites.

    CONCLUSION: ER-induced changes on hepatic metabolomic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.

  • 12. Soderman, Jan
    et al.
    Noren, Elisabeth
    Christiansson, Malin
    Bragde, Hanna
    Thiebaut, Raphaele
    Hugot, Jean-Pierre
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    O'Morain, Colm A.
    Gassull, Miquel
    Finkel, Yigael
    Colombel, Jean-Frederic
    Lemann, Marc
    Almer, Sven
    Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease2013In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 19, no 30, p. 4935-4943Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.

    METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.

    RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.

    CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

  • 13.
    Tysk, Curt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Nyhlin, Nils
    Wickbom, Anna
    Eriksson, Sune
    Diagnosis and management of microscopic colitis2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 48, p. 7280-7288Article in journal (Other academic)
    Abstract [en]

    Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

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