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  • 1.
    Bennet, Sean M. P.
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Polster, Annikka
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Törnblom, Hans
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Isaksson, Stefan
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Capronnier, Sandrine
    Department of Life Science, Danone Nutricia Research, Palaiseau, France.
    Tessier, Aurore
    Department of Life Science, Danone Nutricia Research, Palaiseau, France.
    Le Nevé, Boris
    Department of Life Science, Danone Nutricia Research, Palaiseau, France.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome2016In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 111, no 8, p. 1165-1176Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms.

    METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed.

    RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified.

    CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.

  • 2.
    Dige, Anders
    et al.
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Magnusson, Maria K.
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hvas, Christian Lodberg
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Kelsen, Jens
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Wick, Mary Jo
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Agnholt, Jørgen
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Reduced numbers of mucosal DR(int) macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-α treatment in patients with Crohn's disease2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 6, p. 692-699Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood.

    MATERIAL AND METHODS: Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DR(int) and CD14 (+) DR(hi) MQs, CD141(+), CD141(-) and CD103(+ )DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry.

    RESULTS: At baseline, we observed higher numbers of DR(int) MQs and lower numbers of CD103(+ )DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR(int) MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+ )DCs increased [9-20 × 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4.

    CONCLUSIONS: In CD, mucosal inflammation is associated with high numbers of DR(int) MQs and low numbers of CD103(+ )DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR(int) MQs play a pivotal role in CD inflammation.

  • 3.
    Elmoghazy, Walid
    et al.
    Department of Surgery, Hamad Medical Corporation, Doha, Qatar / Department of Surgery, Sohag University, Sohag, Egypt.
    Ahmed, Khalid
    Department of Surgery, Hamad Medical Corporation, Doha, Qatar.
    Vijay, Adarsh
    Department of Surgery, Hamad Medical Corporation, Doha, Qatar.
    Kamel, Yasser
    Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar.
    Elaffandi, Ahmed
    Department of Surgery, Hamad Medical Corporation, Doha, Qatar / Department of Surgical Oncology, National Cancer Institute, Cairo University, Egypt.
    El Ansari, Walid
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Surgery, Hamad Medical Corporation, Doha, Qatar .
    Kakil, Rasul
    National Center for Cancer Care and Research, Doha, Qatar.
    Khalaf, Hatem
    Department of Surgery, Hamad Medical Corporation, Doha, Qatar.
    Hepatocellular carcinoma in a rapidly growing community: Epidemiology, clinico-pathology and predictors of extrahepatic metastasis2019In: Arab Journal of Gastroenterology, ISSN 1687-1979, Vol. 20, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    Background and study aims: Hepatocellular carcinoma (HCC) with extrahepatic metastasis has been studied, however, data from the Middle East remain scarce. In this study, we assess epidemiology of HCC in Qatar, and identify predictors of the metastatic behaviour. Patients and methods: All newly-diagnosed HCC patients on top of liver cirrhosis between 2011 and 2015 were included in the study. Results: A total of 180 patients met our inclusion criteria. The mean age was 58.8 ± 10.5 years with a mean follow-up of 1.0 ± 1.1 years. There were 150 male patients and HCV was the most common cause of liver cirrhosis 108 (60%), and 22 (12.2%) patients were classified as Child-Pugh class C. The overall survival of 51.1%, and 47 (26%) had at least one extrahepatic metastasis at the time of diagnosis. Single site metastasis was diagnosed in 10 patients, whereas 37 patients had multiple sites metastases. We compared patients who had metastases with patients who did not have metastasis at the time of diagnosis of HCC regarding several variables, and analysis revealed that tumour diameter larger than 5 cm (OR = 6.10, 95% CI = 1.85–20.12) (p = 0.003), and bilobar liver involvement (OR = 5.49, 95% CI = 1.10–27.30) (p = 0.037) were independent predictors of metastatic behaviour of HCC. Conclusion: The incidence of HCC is rising in our population, extrahepatic metastasis is no longer rare and tumours larger than 5 cm and bilobar involvement are determinants of the extrahepatic metastasis. © 2019 Pan-Arab Association of Gastroenterology

  • 4.
    Gunterberg, V.
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, M.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Friberg, P.
    Department of Clinical Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jones, M. P.
    Psychology Faculty, Macquarie University, Sydney, NSW, Australia.
    Van Oudenhove, L.
    Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
    Strid, H.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients2016In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 28, no 11, p. 1655-1662Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC).

    METHODS: We prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years.

    KEY RESULTS: Sympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-α, IFN-γ) and mucosal inflammation (interleukin-8, IFN-γ) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-α. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up.

    CONCLUSIONS & INFERENCES: This study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.

  • 5.
    Jonefjäll, Börje
    et al.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine, Kungälv Hospital, Kungälv, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Center for Functional GI and Motility Disorders, University of North Carolina, USA.
    Strid, Hans
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden.
    IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being2016In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 22, no 11, p. 2630-2640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission.

    METHODS: We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined.

    RESULTS: The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03).

    CONCLUSIONS: IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

  • 6.
    Le Nevé, Boris
    et al.
    Danone Nutricia Research, Life Sciences Department, Palaiseau, France.
    Brazeilles, Rémi
    Danone Nutricia Research, Life Sciences Department, Palaiseau, France.
    Derrien, Muriel
    Danone Nutricia Research, Life Sciences Department, Palaiseau, France.
    Tap, Julien
    Danone Nutricia Research, Life Sciences Department, Palaiseau, France / INRA (Institut National de la Recherche Agronomique) MetaGenoPolis, Jouy en Josas, France.
    Guyonnet, Denis
    Danone Nutricia Research, Life Sciences Department, Palaiseau, France.
    Öhman, Lena
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Törnblom, Hans
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lactulose Challenge Determines Visceral Sensitivity and Severity of Symptoms in Patients With Irritable Bowel Syndrome2016In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 14, no 2, p. 226.e1-233.e3Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) can be assigned to groups with different gastrointestinal (GI) symptoms based on results from a combined nutrient and lactulose challenge. We aimed to identify factors that predict outcomes to this challenge and to determine whether this can be used in noninvasive assessment of visceral sensitivity in patients with IBS.

    METHODS: We performed a prospective study of 100 patients with IBS diagnosed according to Rome III criteria (all subtypes) and seen at a secondary or tertiary care center. After an overnight fast, subjects were given a liquid breakfast (400 mL; Nutridrink) that contained 25 g lactulose. Before the challenge, we assessed visceral sensitivity (via rectal barostat), oro-anal transit time, and fecal microbiota composition (via 16S ribosomal RNA pyrosequencing); we determined IBS severity using questionnaires. The intensity of 8 GI symptoms, the level of digestive comfort, and the amount of exhaled H2 and CH4 in breath were measured before and during a 4-hour period after the liquid breakfast.

    RESULTS: Based on the intensity of 8 GI symptoms and level of digestive comfort during the challenge, patients were assigned to groups with high-intensity GI symptoms (HGS; n = 39) or low-intensity GI symptoms (LGS; n = 61); patients with HGS had more severe IBS (P < .0001), higher somatization (P < .01), and lower quality of life (P < .05-.01) than patients with LGS. Patients with HGS also had significantly higher rectal sensitivity to random phasic distensions (P < .05-.001, compared with patients with LGS). There were no significant differences between groups in fecal microbiota composition, exhaled gas in breath, or oro-anal transit time.

    CONCLUSIONS: We found, in a prospective study, that results from a lactulose challenge test could be used to determine visceral sensitivity and severity of IBS. The intensity of patient symptoms did not correlate with the composition of the fecal microbiota. The lactulose challenge test may help better characterize patients with IBS and evaluate the efficacy of new treatments. ClinicalTrial.gov no: NCT01252550.

  • 7.
    Lebrero-Fernandez, Cristina
    et al.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Wenzel, Ulf Alexander
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Akeus, Paulina
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Wang, Ying
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Strid, Hans
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden / Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA.
    Gustavsson, Bengt
    Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Börjesson, Lars G.
    Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Cardell, Susanna L.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Quiding-Järbrink, Marianne
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Bas-Forsberg, Anna
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Altered expression of Butyrophilin (BTN) and BTN-like (BTNL) genes in intestinal inflammation and colon cancer2016In: Immunity, Inflammation and Disease, ISSN 2050-4527, Vol. 4, no 2, p. 191-200Article in journal (Refereed)
    Abstract [en]

    Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2(-/-)) and intestinal tumorigenesis (Apc(Min/+)). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially BTN1A1, BTN2A2, BTN3A3, and BTNL8 were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of BTNL2, BTNL3, BTNL8, and BTNL9 as compared to unaffected tissue. Colonic inflammation in Muc2(-/-) mice significantly down-regulated the expression of particularly Btnl1, Btnl4, and Btnl6 mRNA, and intestinal polyps derived from Apc(Min/+) mice displayed altered levels of Btn1a1, Btn2a2, and Btnl1 transcripts. Thus, our data present an association of BTN and BTNL genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.

  • 8.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Brynjólfsson, Siggeir F.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Dige, Anders
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Uronen-Hansson, Heli
    Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Börjesson, Lars G.
    Department of Surgery, Sahlgrenska University Hospital, Gotenburg, Sweden.
    Bengtsson, Jonas L.
    Department of Surgery, Sahlgrenska University Hospital, Gotenburg, Sweden.
    Gudjonsson, Sigurdur
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Öhman, Lena
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Agnholt, Jørgen
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Sjövall, Henrik
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Agace, William W.
    Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden / Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
    Wick, Mary Jo
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation2016In: Mucosal Immunology, ISSN 1933-0219, E-ISSN 1935-3456, Vol. 9, no 1, p. 171-182Article in journal (Refereed)
    Abstract [en]

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14(+)DR(int) MQs characterized inflamed intestinal mucosa while total CD141(+) or CD1c(+) DCs numbers were unchanged. However, CD103(+) DCs, including CD141(+)CD103(+) and CD1c(+)CD103(+) DCs, were reduced in inflamed intestine. In MLNs, two CD14(-) DC populations were identified: CD11c(int)HLADR(hi) and CD11c(hi)HLADR(int) cells. A marked increase of CD11c(hi)HLADR(int) DC, particularly DR(int)CD1c(+) DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH(+) cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.

  • 9.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Strid, Hans
    Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden.
    Isaksson, Stefan
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Swede.
    The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 956-966Article in journal (Refereed)
    Abstract [en]

    Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.

  • 10.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Strid, Hans
    Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden / Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden.
    Sapnara, Maria
    Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Lasson, Anders
    Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden.
    Bajor, Antal
    Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden / Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden .
    Ung, Kjell-Arne
    Kärnsjukhuset, Department of Internal Medicine, Skövde, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 8, p. 943-952Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.

    METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline.

    RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders.

    CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

  • 11.
    Tap, Julien
    et al.
    Danone Nutricia Research, Palaiseau, France / French National Institute for Agricultural Research (INRA) MetaGenoPolis, Jouy en Josas, France.
    Derrien, Muriel
    Danone Nutricia Research, Palaiseau, France.
    Törnblom, Hans
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Centre for Person-Centered Care, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Brazeilles, Rémi
    Danone Nutricia Research, Palaiseau, France.
    Cools-Portier, Stéphanie
    Danone Nutricia Research, Palaiseau, France.
    Doré, Joël
    French National Institute for Agricultural Research (INRA) MetaGenoPolis, Jouy en Josas, France.
    Störsrud, Stine
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Le Nevé, Boris
    Danone Nutricia Research, Palaiseau, France.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Centre for Person-Centered Care, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina, USA.
    Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 152, no 1, p. 111-123.e8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms.

    METHODS: We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at secondary or tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H2 and CH4, oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numeric ecology analyses and a machine learning procedure were used to analyze the data.

    RESULTS: Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with vs without IBS. A computational statistical technique-like machine learning procedure allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications.

    CONCLUSIONS: In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms.

    TRIAL REGISTRATION NUMBER: NCT01252550.

  • 12.
    Toffaha, Ali
    et al.
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Elaiwy, Orwa
    Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
    Obaid, Munzir
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Al-Yahri, Omer
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Abdelazim, Sherif
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    First sliding Amyand hernia harbouring appendicular schistosomiasis: Case report2019In: International journal of surgery case reports, ISSN 2210-2612, E-ISSN 2210-2612, Vol. 63, p. 143-146Article in journal (Refereed)
    Abstract [en]

    Introduction: Amyand's hernia (AH) is rare, schistosomiasis of the appendix is very uncommon, and both conditions coexisting together is an extremely rare event. Pre-operative diagnosis of each of the two conditions is usually difficult. To the best of our knowledge, the current paper is first to report both these two conditions in coexistence. Presentation of case: A 31-year old man who had no comorbidities was admitted electively as a day case of non-complicated right indirect inguinal hernia. Further history and physical examination were unremarkable. Intraoperatively the patient was found to have right sliding AH with appendicular schistosomiasis (AS). The patient underwent Lichtenstein repair of the hernia with appendectomy. On follow up he was referred to infectious disease clinic, and the post-operative course was uneventful. Conclusions: Intraoperative identification of non-typical hernia sac before its opening should alert the surgeon to the possibility of sliding hernia and the presence of an organ as a part of the sac. Rare causes of appendicular masses like schistosomiasis granuloma should be considered in endemic areas or immigrants from these areas, despite the difficulty of preoperative diagnosis. Management should follow general guidelines of appendectomy, hernia repair and dealing with the associated pathology if present. 

  • 13.
    Toffaha, Ali
    et al.
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Ramzee, Ahmed Faidh
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Afana, Mohammad
    Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar.
    Aljohary, Hesham
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Rare presentation of primary varicella zoster as fatal fulminant hepatitis in adult on low-dose, short-term steroid: Case report2019In: Annals of Medicine and Surgery, ISSN 2049-0801, Vol. 48, p. 115-117Article in journal (Refereed)
    Abstract [en]

    Background: Varicella zoster virus presents clinically as primary (chickenpox) or secondary (herpes zoster) infection. Cutaneous and extracutaneous dissemination may occur, usually in immunocompromised patients. VZV hepatitis that progresses to fulminant hepatic failure is very rare and fatal. To the best of our knowledge, 9 cases have been reported to date, of which 7 were in immunocompromised adults, and only one patient was on short duration steroid therapy. Presentation of case: We present a 26-year old man who was admitted initially with acute abdomen as query persistent biliary colic. Later, he showed clinical and laboratory findings of VZV hepatitis that progressed rapidly despite maximal medical ICU support and he expired on day 3 of admission. Conclusions: Acute VZV infection may present as fulminant hepatitis. The presentation may initially be challenging for the diagnosis and should be considered if the patient has been in contact with a sick case. Low dose corticosteroid could carry a risk for fatal VZV fulminant hepatitis and should be used very cautiously especially with VZV patients’ contacts. Further causative relationships remain to be established. 

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