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Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation

Journal article
Authors Sean Bennet
Johanna Sundin
Maria K Magnusson
H. Strid
J. Tap
M. Derrien
B. Le Neve
J. Dore
Hans Törnblom
Magnus Simrén
Lena Öhman
Published in Neurogastroenterology and Motility
Volume 30
Issue 12
ISSN 1350-1925
Publication year 2018
Published at University of Gothenburg Centre for person-centred care (GPCC)
Institute of Biomedicine
Institute of Medicine
Language en
Links dx.doi.org/10.1111/nmo.13468
Keywords antimicrobial peptide, intestinal, microbiota, ulcerative-colitis, innate immunity, microbiota, disorders, disease, ibs, inflammation, recognition, kinases, Gastroenterology & Hepatology, Neurosciences & Neurology, hroeder kw, 1987, new england journal of medicine, v317, p1625, ates of america, v107, p454, crobiology, v59, p1895, ates of america, v104, p6764
Subject categories Internal medicine

Abstract

Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.

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