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Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome

Authors Olbjørn C, Cvancarova Småstuen M, Thiis-Evensen E, Nakstad B, Vatn MH, Jahnsen J, Ricanek P, Vatn S, Moen AEF, Tannæs TM, Lindstrøm JC, Söderholm JD, Halfvarson J, Gomollón F, Casén C, Karlsson MK, Kalla R, Adams AT, Satsangi J, Perminow G

Received 5 September 2018

Accepted for publication 13 December 2018

Published 31 January 2019 Volume 2019:12 Pages 37—49


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Koulaouzidis

Christine Olbjørn,1,2 Milada Cvancarova Småstuen,3 Espen Thiis-Evensen,4 Britt Nakstad,1,2 Morten Harald Vatn,5 Jørgen Jahnsen,2,6 Petr Ricanek,2,6 Simen Vatn,2,6 Aina EF Moen,5 Tone M Tannæs,5 Jonas C Lindstrøm,7 Johan D Söderholm,8 Jonas Halfvarson,9 Fernando Gomollón,10 Christina Casén,11 Magdalena K Karlsson,11 Rahul Kalla,12 Alex T Adams,12,13 Jack Satsangi,12,13 Gøri Perminow14

1Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway; 2Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway; 3Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway; 4Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 5Department of Clinical Molecular Biology (EpiGen), Division of Medicine, Akershus University Hospital, Lørenskog, and University of Oslo, Oslo, Norway; 6Department of Gastroenterology, Akerhus University Hospital, Lørenskog, Norway; 7Institute of Clinical Medicine, University of Oslo, Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway; 8Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 9Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden; 10Digestive Diseases Unit, IIS Aragón, Zaragoza, Spain; 11Genetic-Analysis AS, Oslo, Norway; 12Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; 13Translational Gastroenterology Unit, Experimental Medicine Division, University of Oxford, Oxford, UK; 14Department of Pediatrics, Oslo University Hospital, Ullevål, Oslo, Norway

Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naïve IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes.
Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohn’s disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map™ technology at diagnosis and after therapy in IBD patients.
Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (P<0.001). Only Prevotella was more abundant in patients (P<0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (P<0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (P<0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (P<0.01), and nonmucosal healing (P<0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (P<0.03). After therapy, IBD patients had unchanged dysbiosis.
Conclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.

Keywords: dysbiosis, Crohn’s disease, ulcerative colitis, Proteobacteria, biologic therapy, Faecalibacterium prausnitzii

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