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The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis

Journal article
Authors Maria K Magnusson
Hans Strid
Stefan Isaksson
Magnus Simrén
Lena Öhman
Published in Inflammatory Bowel Diseases
Volume 23
Issue 6
Pages 956-966
ISSN 1078-0998
Publication year 2017
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 956-966
Language en
Links 10.1097/mib.0000000000001130
Keywords ulcerative colitis, antibacterial response, microbiota, inflammatory-bowel-disease, permeability-increasing protein, clinical-course, colonic-mucosa, new-onset, lipopolysaccharide, autoantibodies, binding, bpi, predictors
Subject categories Gastroenterology and Hepatology, Internal medicine

Abstract

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.

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