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  • 1.
    Edebol Carlman, Hanna M. T.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology. Center for Applied Autonomous Sensor Systems.
    Pruessner, Jens C.
    Douglas Institute, McGill University, Montréal, QC H4H1R3, Canada; Department of Psychology, University of Konstanz, Konstanz, Germany.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 7, article id 1329Article in journal (Refereed)
    Abstract [en]

    Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

  • 2.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Lathrop Stern, Lori
    Labus, Jennifer
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Evaluating the effects of probiotic intake on brain activity during an emotional attention task and blood markers related to stress in healthy subjects2019Conference paper (Refereed)
  • 3.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Pruessner, Jens C.
    McGill Centre for Studies in Ageing, Department of Psychology, Psychiatry, Neurology and Neurosurgery, Douglas Institute, McGill University, Montréal, Canada.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects brain responses to an arithmetic stress task in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 4.
    Fröhlich, Julia D
    et al.
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; Department of Obstetrics & Gynaecology, Medical University of Graz, Graz, Austria.
    Huppertz, Berthold
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Abuja, Peter M
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    König, Julia
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Desoye, Gernot
    Department of Obstetrics & Gynaecology, Medical University of Graz, Graz, austria.
    Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia2012In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 180, no 1, p. 153-164Article in journal (Refereed)
    Abstract [en]

    Pregestational diabetes retards early embryonic growth. Placental and fetal growth are closely associated, suggesting that placental growth is also impaired. During the first trimester of gestation, oxygen tension rises steeply, leading to excessive production of reactive oxygen species (ROS), which is exacerbated in diabetes and may affect placental development. We hypothesized that oxygen modifies hyperglycemic effects on ROS formation, resulting in decreased first-trimester trophoblast growth. This was tested using a first trimester trophoblast-derived cell line (ACH-3P). Normoglycemia did not alter ACH-3P proliferation at 2.5%, 8%, and 21% oxygen. Hyperglycemic conditions for up to 3 days reduced cell number by 65% and resulted in cell cycle (G(1)- and S-phase) changes but only at 21% oxygen. Proliferation reduction could be partially restored by an inhibitor of mitogen-activated protein kinase (MAPK) ERK1/2 but not of Akt/PkB. Intracellular ROS elevation under hyperglycemia was oxygen independent, whereas mitochondrial superoxide levels were enhanced under hyperglycemia only at 21% oxygen. Intervention to modulate cytosolic and mitochondrial ROS, using ROS formation inducers and inhibitors, did not alter cell growth under hyperglycemia at 21% oxygen. The combination of hyperglycemia and high oxygen levels (21%) reduces proliferation of human first-trimester trophoblasts in a ROS-independent manner involving MAPK. This may account for reduced placental growth and, therefore, also for embryonic growth during the first-trimester pregestational diabetic pregnancies when the oxygen tension increases.

  • 5.
    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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  • 6.
    Holster, S.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, D.
    Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Salonen, A.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Rajan, Sukithar K
    Örebro University, School of Medical Sciences.
    De Vos, W. M.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, The Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndromeManuscript (preprint) (Other academic)
  • 7.
    Holster, S.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, D.
    Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Salonen, A.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Rajan, Sukithar K
    Örebro University, School of Medical Sciences.
    de Vos, W. M.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, the Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome2021In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 12, no 1, p. 17-30Article in journal (Refereed)
    Abstract [en]

    Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.

  • 8.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Fecal Microbiota Transplantation in Irritable Bowel Syndrome and a Randomized Placebo-Controlled Trial2017In: 2017 DDW Abstracts, Saunders Elsevier, 2017, Vol. 152, no 5, p. S101-S102Conference paper (Other academic)
  • 9.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Hooiveld, Guido J.
    Nutrition, Metabolism and Genomics group, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    de Vos, Willem
    Laboratory of Microbiology, Wageningen University and Research Centre and Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome2019In: Biomolecules, E-ISSN 2218-273X, Vol. 9, no 10, article id 586Article in journal (Refereed)
    Abstract [en]

    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe–host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

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    Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
  • 10.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Salonen, Anne
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    de Vos, Willem
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, the Netherlands.
    König, Julia
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study2019In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 10, no 4, article id e00034Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.

    METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.

    RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P 5 0.02), which was not the case in the autologous group (P50.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor’s fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.

    CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.

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    The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study
  • 11.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in irritable bowel syndrome: clinical outcomes of a randomised placebo-controlled trial2017In: UEG Week 2017 Oral Presentations, Sage Publications, 2017, Vol. 5, p. A155-A156Conference paper (Refereed)
  • 12.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, Dawei
    Science and Engineering, School of Science and Technology, Örebro University, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    de Vos, W.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, The Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in irritable bowel syndrome results inaltered correlations between the gut microbiota and its metabolitesManuscript (preprint) (Other academic)
  • 13.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Kumawat, Ashok Kumar
    Örebro University, School of Medical Sciences.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in patients with microscopic colitis: A proof-of-concept study in collagenous colitisManuscript (preprint) (Other academic)
  • 14.
    Holster, Savanne
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Gastroenterology.
    Kumawat, Ashok Kumar
    Örebro University, School of Medical Sciences.
    Veress, Gábor
    Department of Laboratory Medicine, Faculty for Medicine and Health, Örebro University, Örebro, Sweden; Örebro University Hospital, Örebro, Swed.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in patients with microscopic colitis: a pilot study in collagenous colitis2020In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 55, no 12, p. 1454-1466Article in journal (Refereed)
    Abstract [en]

    Objectives: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota.

    Methods: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors.

    Results: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed.

    Conclusions: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.

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    Faecal microbiota transfer in patients with microscopic colitis – a pilot study in collagenous colitis
  • 15.
    Huppertz, Berthold
    et al.
    Institute of Cell Biology, Histology and Embryology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
    Gauster, Martin
    Institute of Cell Biology, Histology and Embryology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
    Orendi, Kristina
    Institute of Cell Biology, Histology and Embryology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
    König, Julia
    Institute of Cell Biology, Histology and Embryology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
    Moser, Gerit
    Institute of Cell Biology, Histology and Embryology, Centre of Molecular Medicine, Medical University of Graz, Graz, Austria.
    Oxygen as modulator of trophoblast invasion2009In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 215, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    At the time of blastocyst implantation the uterine spiral arteries have already undergone morphological changes in the absence of any extravillous trophoblast invasion. Only 2 weeks after implantation, extravillous trophoblast cells develop and come into first contact with decidual tissues. Invading through the decidual interstitium, extravillous trophoblasts potentially reach and transform spiral arteries into uteroplacental arteries. Spiral arterial erosion starts at about mid-first trimester, whereas flow of maternal blood into the intervillous space is continuously established only at the beginning of the second trimester. One key regulator of the number of extravillous trophoblasts is oxygen. The steep gradient in oxygen concentration within the first trimester placenta is diminished with the onset of maternal blood flow. This gradient is used by the trophoblast to generate a large number of invasive cells to adapt the arterial vasculature in the placental bed to the growing needs of the fetus. Changes in oxygen concentrations or other factors leading to alterations in the rates of proliferation and/or apoptosis of extravillous trophoblast clearly impact on the remodelling of the vessels. The respective consequences of a failure in trophoblast invasion are growth restrictions of the baby and perhaps other pregnancy complications.

  • 16.
    Kinzer, M.
    et al.
    Institute of Cell Biology, Histology and Embryology, Med Univ Graz, Graz, Austria.
    Hingerl, K.
    Institute of Cell Biology, Histology and Embryology, Med Univ Graz, Graz, Austria.
    König, Julia
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Cell Biology, Histology and Embryology, Med Univ Graz, Graz, Austria.
    Reinisch, A.
    Department of Internal Medicine, Stem Cell Research Unit, Division of Hematology, Med Univ Graz, Graz, Austria.
    Strunk, D.
    Experimental & Clinical Cell Therapy Institute, Spinal Cord & Tissue Regeneration Center, Paracelsus Med Univ, Salzburg, Austria.
    Huppertz, B.
    Institute of Cell Biology, Histology and Embryology, Med Univ Graz, Graz, Austria.
    Lang, I.
    Institute of Cell Biology, Histology and Embryology, Med Univ Graz, Graz, Austria.
    Mesenchymal stromal cells from the human placenta promote neovascularization in a mouse model in vivo.2014In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 35, no 7, p. 517-519Article in journal (Refereed)
    Abstract [en]

    Cell transplantation is a promising strategy in regenerative medicine for revascularization of ischemic tissues. Based on our observation that placental mesenchymal stromal cells (PMSC) enhance endothelial cell viability in vitro via secretion of angiogenic factors, we asked whether PMSC support vascular growth in vivo. PMSC were isolated from amnion and placental endothelial cells (PLEC) from chorion and either separately or co-transplanted subcutaneously into immune-deficient mice. Co-transplantation resulted in a higher number of perfused human vessels (CD31+/vimentin+) containing mouse glycophorin A+ erythrocytes. Results indicate positive effects of PMSC on neovascularization in vivo, making them attractive candidates to create autologous PMSC/PLEC pairs for research and transplantation.

  • 17.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Faecal microbiota transplantation in IBS: new evidence for success?2020In: Nature Reviews. Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 17, no 4, p. 199-200Article in journal (Refereed)
    Abstract [en]

    Faecal microbiota transplantation (FMT) aims to restore an altered microbiota and has been suggested as a potential treatment option for irritable bowel syndrome (IBS), among other diseases. A new study suggests that the use of a so-called superdonor is necessary to successfully treat patients with IBS using FMT.

  • 18.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Is an enzyme supplement for celiac disease finally on the cards?2018In: Expert Review of Gastroenterology & Hepatology, ISSN 1747-4124, E-ISSN 1747-4132, Vol. 12, no 6, p. 531-533Article in journal (Refereed)
  • 19.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert-Jan
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome2014In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 5, no 3, p. 247-261Article, review/survey (Refereed)
    Abstract [en]

    The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation.

  • 20.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert-Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    Modulation of the gut ecosystem in irritable bowel syndrome2014In: Pharma-Nutrition: an overview / [ed] Gert Folkerts, Johan Garssen, Springer, 2014, p. 55-73Chapter in book (Refereed)
  • 21.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ganda-Mall, John-Peter
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Edebol-Carlman, Hanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    The Role of the Gut Microbiota in Brain Function2015In: Probiotics and Prebiotics: Current Research and Future Trends / [ed] Koen Venema & Ana Paula do Carmo, Poole, UK: Caister Academic Press, 2015Chapter in book (Refereed)
  • 22.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Bruins, Maaike
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Aspergillus Niger-Derived Enzyme Degrades Gluten in the Stomach of Gluten-Sensitive Subjects2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 152, no 5, Suppl.1, p. S481-S481Article in journal (Refereed)
  • 23.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Bruins, Maaike
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Effective gluten degradation in non-coeliac gluten-sensitive subjects by Aspergillus Niger derived enzyme: A placebo-controlled randomized clinical trial2017Conference paper (Refereed)
  • 24.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Maaike, Bruins
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, no 13100Article in journal (Refereed)
    Abstract [en]

    The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.

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  • 25.
    König, Julia
    et al.
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Huppertz, Berthold
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Desoye, Gernot
    Clinic of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
    Parolini, Ornella
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero, Brescia, Italy.
    Fröhlich, Julia D
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; Clinic of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
    Weiss, Gregor
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Dohr, Gottfried
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Sedlmayr, Peter
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Lang, Ingrid
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells2012In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 21, no 8, p. 1309-1320Article in journal (Refereed)
    Abstract [en]

    Mesenchymal stromal cells derived from the human amnion (hAMSC) currently play an important role in stem cell research, as they are multipotent cells that can be isolated using noninvasive methods and are immunologically tolerated in vivo. The objective of this study was to evaluate their endothelial differentiation potential with regard to a possible therapeutic use in vascular diseases. hAMSC were isolated from human term placentas and cultured in Dulbecco's modified Eagle's medium (DMEM) (non-induced hAMSC) or endothelial growth medium (EGM-2) (induced hAMSC). Induced hAMSC changed their fibroblast-like toward an endothelial-like morphology, and were able to take up acetylated low-density lipoprotein and form endothelial-like networks in the Matrigel assay. However, they did not express the mature endothelial cell markers von Willebrand factor and vascular endothelial-cadherin. Gene expression analysis revealed that induced hAMSC significantly downregulated pro-angiogenic genes such as tenascin C, Tie-2, vascular endothelial growth factor A (VEGF-A), CD146, and fibroblast growth factor 2 (FGF-2), whereas they significantly upregulated anti-angiogenic genes such as serpinF1, sprouty1, and angioarrestin. Analysis of protein expression confirmed the downregulation of FGF-2 and Tie-2 (27%±8% and 13%±1% of non-induced cells, respectively) and upregulation of the anti-angiogenic protein endostatin (226%±4%). Conditioned media collected from hAMSC enhanced viability of endothelial cells and had a stabilizing effect on endothelial network formation as shown by lactate dehydrogenase and Matrigel assay, respectively. In summary, endothelial induced hAMSC acquired some angiogenic properties but resisted undergoing a complete differentiation into mature endothelial cells by upregulation of anti-angiogenic factors. Nevertheless, they had a survival-enhancing effect on endothelial cells that might be useful in a variety of cell therapy or tissue-engineering approaches.

  • 26.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Inst Cell Biol Histol & Embryol, Med Univ Graz, Graz, Austria.
    Lang, Ingrid
    Inst Cell Biol Histol & Embryol, Med Univ Graz, Graz, Austria.
    Siwetz, Monika
    Inst Cell Biol Histol & Embryol, Med Univ Graz, Graz, Austria.
    Fröhlich, Julia
    Inst Cell Biol Histol & Embryol, Med Univ Graz, Graz, Austria.
    Huppertz, Berthold
    Inst Cell Biol Histol & Embryol, Med Univ Graz, Graz, Austria.
    Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype in culture.2014In: Cell and Tissue Banking, ISSN 1389-9333, E-ISSN 1573-6814, Vol. 15, no 2, p. 193-198Article in journal (Refereed)
    Abstract [en]

    The amnionic membrane is a rich source of multipotent mesenchymal stromal cells (hAMSC), which are readily available and show a potential use in regenerative medicine and tissue engineering. Before these cells can be applied clinically, careful characterization is necessary, especially as primary cells are known to change their phenotype in culture. We analyzed the mesenchymal phenotype of hAMSC at different stages after isolation using immunohistochemistry. Shortly after isolation (1 day), 92 % (±7 %) of the hAMSC expressed the mesenchymal marker vimentin, 2 % (±1 %) stained for the epithelial marker cytokeratin-7 and 5 % (±4 %) co-expressed these markers. After 5 days, the double positive cells slightly increased to 7 % (±3 %), while exclusive expression of cytokeratin-7 or vimentin remained unchanged (1 % ± 2 % and 92 % ± 1 %, respectively). After the first passage, all attached cells were vimentin-positive, while 54 % (±9 %) co-expressed cytokeratin-7 and vimentin. Thus, we conclude that under culture, hAMSC adopt a hybrid mesenchymal-epithelial phenotype. It is also essential to perform microscopical examination during the first days after isolation to detect contaminations with human amnion-derived epithelial cells in cultures of hAMSC.

  • 27.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medicine, Örebro University, Sweden.
    The Role of Lactic Acid Bacteria in the Pathophysiology and Treatment of Irritable Bowel Syndrome (IBS)2013In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, Vol. 4, no 11, p. 27-39Article, review/survey (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a multifactorial chronic disorder characterized by various abdominal complaints and a worldwide prevalence of 10% - 20%. Although its etiology and pathophysiology are complex and still not completely understood, aberrations along the microbe-gut-brain axis are known to play a central role. IBS is characterized by inter-related alterations in intestinal barrier function, gut microbe composition, immune activation, afferent sensory signaling and brain activity. Pharmaceutical treatment is generally ineffective and, hence, most therapeutic strategies are based on non-drug approaches. A promising option is the administration of probiotics, in which lactic acid bacteria strains are considered specifically beneficial. This review aims to provide a concise, although comprehensive, overview of the role of lactic acid bacteria in the pathophysiology and treatment of IBS.

  • 28.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Siebenhaar, A.
    Hamburg, Germany.
    Högenauer, C.
    Graz, Austria.
    Arkkila, P.
    Helsinki, Finland.
    Nieuwdorp, M.
    Amsterdam, The Netherlands; Gothenburg, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences.
    Ponsioen, C. Y.
    Amsterdam, The Netherlands.
    Rosien, U.
    Hamburg, Germany.
    Rossen, N. G.
    Amsterdam, The Netherlands.
    Satokari, R.
    Helsinki, Finland.
    Stallmach, A.
    Jena, Germany.
    de Vos, W.
    Helsinki, Finland; Wageningen, The Netherlands.
    Keller, J.
    Hamburg, Germany.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Consensus report: Faecal microbiota transfer - clinical applications and procedures2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 2, p. 222-239Article, review/survey (Refereed)
    Abstract [en]

    Background: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.

    Aim: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.

    Methods: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.

    Results: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.

    Conclusions: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.

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  • 29.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Weiss, Gregor
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
    Rossi, Daniele
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Brescia, Italy.
    Wankhammer, Karin
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria .
    Reinisch, Andreas
    Stem Cell Research Unit, Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria..
    Kinzer, Manuela
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
    Huppertz, Berthold
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Pfeiffer, Dagmar
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Parolini, Ornella
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Brescia, Italy.
    Lang, Ingrid
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?2014In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 24, no 1, p. 115-131Article in journal (Refereed)
    Abstract [en]

    Mesenchymal stromal cells (MSCs) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSCs from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells (ECs). We hypothesize that MSCs derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSCs from placental chorionic blood vessels (bv-MSCs) and tested their angiogenic potential in comparison to amnion-derived avascular MSCs (av-MSCs). bv-MSCs express a very similar surface marker profile compared with av-MSCs and could be differentiated toward the adipogenic and osteogenic lineages. bv-MSCs exert immunosuppressive properties on peripheral blood mononuclear cells, suggesting that they are suitable for cell transplantation settings. Conditioned medium (Cdm) from av-MSCs and bv-MSCs significantly enhanced EC viability, whereas only Cdm from bv-MSCs significantly increased EC migration and network formation (Matrigel assay). Angiogenesis array analysis of av- and bv-MSC-Cdm revealed a similar secretion pattern of angiogenic factors, including angiogenin, interleukins-6 and -8, and tissue inhibitors of matrix metalloproteinase-1 and 2. Enzyme-linked immunosorbent assay analysis showed that, in contrast to av-MSCs, bv-MSCs secreted vascular endothelial growth factor. In direct coculture with bv-MSCs, ECs showed a significantly increased formation of vessel-like structures compared with av-MSCs. With regard to therapeutic treatment, bv-MSCs and particularly their Cdm might be valuable to stimulate angiogenesis especially in ischemic tissues. av-MSCs and their Cdm could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.

  • 30.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Wells, Jerry
    Host–Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands.
    Cani, Patrice D.
    Metabolism and Nutrition Research Group, WELBIO—Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    García-Ródenas, Clara L.
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    MacDonald, Tom
    Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
    Mercenier, Annick
    Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
    Whyte, Jacqueline
    European Branch, The International Life Sciences Institute, Brussels, Belgium.
    Troost, Freddy
    Division of Gastroenterology-Hepatology, Department of Internal Medicine, University Hospital Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
    Brummer, Robert-Jan
    Örebro University, School of Medical Sciences.
    Human Intestinal Barrier Function in Health and Disease2016In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 7, no 10, article id e196Article, review/survey (Refereed)
    Abstract [en]

    The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed.

  • 31.
    Marques, Tatiana M.
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Correlating the gut microbiome to health and disease2016In: The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota / [ed] Niall Hyland, Catherine Stanton, Elsevier, 2016, p. 261-291Chapter in book (Refereed)
    Abstract [en]

    The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus it plays a vital role for the host’s health. Our understanding of the effect of the gut microbiome in health and disease has grown substantially over the past 2 decades, mostly because of recent advances in sequencing and other high-throughput technologies. Given its high metabolic potential, close proximity to the intestinal mucosa, and interaction with the immune system, it is not surprising that the gut microbiome is an important partaker in human health. Evidence to the importance of the gut microbiome in human health and disease is the growing number of conditions now linked to changes in the resident gut microbiota, including recurrent Clostridium difficile infections, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, allergies, neurological diseases, and metabolic diseases. Research into this field of the association of the gut microbiome with health and disease continues to expand at a rapid pace as we come to accept the gut microbiome as our “second genome.” Targeting the gut microbiome to restore/modulate its composition with the use of antibiotics, probiotics, prebiotics, and even fecal microbiota transplantation is considered a promising future strategy for the development of new solutions in the treatment of various diseases associated with an imbalance in microbiota composition and functioning.

  • 32.
    Roca Rubio, Maria Fernanda
    et al.
    Örebro University, School of Medical Sciences.
    Eriksson, Ulrika
    Örebro University, School of Science and Technology.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Sauna dehydration as a new physiological challenge model for intestinal barrier function2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 15514Article in journal (Refereed)
    Abstract [en]

    The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

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    Sauna dehydration as a new physiological challenge model for intestinal barrier function
  • 33.
    Roca Rubio, Maria Fernanda
    et al.
    Örebro University, School of Medical Sciences.
    Eriksson, Ulrika
    Örebro University, School of Science and Technology.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Short intense psychological stress induced by skydiving does not impair intestinal barrier function2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 7, article id e025428Article in journal (Refereed)
    Abstract [en]

    Background and aim: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function.

    Materials and methods: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018.

    Results: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes.

    Discussion: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.

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    Short intense psychological stress induced by skydiving does not impair intestinal barrier function
  • 34.
    Roca Rubio, Maria Fernanda
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Forsgård, Richard A.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brummer, Robert J.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Markers of intestinal barrier function in diarrhoea-predominant irritable bowel syndrome: Correlations and individual variationsManuscript (preprint) (Other academic)
  • 35.
    Roca Rubio, Maria Fernanda
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kremp, Carolin
    Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Folkesson, Mattias
    Örebro University, School of Health Sciences. Division of Sports Sciences, School of Health Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Evertsson, Niklas
    Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ganda Mall, John-Peter
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kadi, Fawzi
    Örebro University, School of Health Sciences. Division of Sports Sciences, School of Health Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brummer, Robert
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challengeManuscript (preprint) (Other academic)
  • 36.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol Carlman, Hanna M. T.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 18, article id 2922Article in journal (Refereed)
    Abstract [en]

    Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p &lt; 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR &lt; 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.

  • 37.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol Carlman, Hanna M. T.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Andersson, Pernilla
    Örebro University, School of Law, Psychology and Social Work.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Lathrop Stern, Lori
    Global Medical Innovation, Pfizer Consumer Healthcare, Madison, NJ, United States.
    Salomon, Benita
    Örebro University, School of Medical Sciences.
    Mohammed, Ahmed Abdulilah
    Department of Radiology and Medical Physics, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Labus, Jennifer S.
    Integrative Bioinformatics and Biostatistics Core, Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial2022In: Frontiers in nutrition, E-ISSN 2296-861X, Vol. 9, article id 827182Article in journal (Refereed)
    Abstract [en]

    Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.

    Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.

    Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.

    Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.

    Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.

    Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].

  • 38.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol-Carlman, Hanna
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects resting state brain function in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 39.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Edebol-Carlman, Hanna
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Andersson, Pernilla
    Örebro University, School of Law, Psychology and Social Work.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Lathrop Stern, Lori
    Global Medical Innovation, Pfizer Consumer Healthcare, Madison, NJ, USA.
    Salomon, Benita
    Örebro University, School of Medical Sciences.
    Abdulilah Mohammed, Ahmed
    Faculty of Medicine and Health, Department of Radiology, Örebro University, Örebro, Sweden.
    Labus, Jennifer S.
    Bioinformatics and Neuroimaging Core, Oppenheimer Center for Neurobiology of Stress and Resilience, David Geffen School of Medicine at UCLA, Los Angeles, USA.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects brain responses towards an emotional task in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 40.
    Rode, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Yang, Lin
    Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    Venizelos, Nikolaos
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Vumma, Ravi
    Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
    Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders2021In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 80, no 3, p. 253-263Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions.

    OBJECTIVE: Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives.

    METHODS: Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (3H) was used as a tracer to measure the transport of tryptophan across the cell membranes (n = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (n = 2).

    RESULTS: As hypothesized,oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan.

    CONCLUSIONS: Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.

1 - 40 of 40
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