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

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 Jona...

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Main 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
Format: Article
Language:English
Published: Dove Medical Press 2019-01-01
Series:Clinical and Experimental Gastroenterology
Subjects:
Online Access:https://www.dovepress.com/fecal-microbiota-profiles-in-treatment-naive-pediatric-inflammatory-bo-peer-reviewed-article-CEG
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author 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
author_facet 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
author_sort Olbjørn C
collection DOAJ
description 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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spelling doaj.art-c56efebc4ec546039f7e2b7171c994792022-12-22T02:10:01ZengDove Medical PressClinical and Experimental Gastroenterology1178-70232019-01-01Volume 12374943856Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcomeOlbjørn CCvancarova Småstuen MThiis-Evensen ENakstad BVatn MHJahnsen JRicanek PVatn SMoen AEFTannæs TMLindstrøm JCSöderholm JDHalfvarson JGomollón FCasén CKarlsson MKKalla RAdams ATSatsangi JPerminow GChristine 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 prausnitziihttps://www.dovepress.com/fecal-microbiota-profiles-in-treatment-naive-pediatric-inflammatory-bo-peer-reviewed-article-CEGdysbiosisCrohn´s diseaseulcerative colitisProteobacteriabiologic therapyFaecalibacterium prausnitzii
spellingShingle 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
Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
Clinical and Experimental Gastroenterology
dysbiosis
Crohn´s disease
ulcerative colitis
Proteobacteria
biologic therapy
Faecalibacterium prausnitzii
title Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
title_full Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
title_fullStr Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
title_full_unstemmed Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
title_short Fecal microbiota profiles in treatment-naïve pediatric inflammatory bowel disease – associations with disease phenotype, treatment, and outcome
title_sort fecal microbiota profiles in treatment na iuml ve pediatric inflammatory bowel disease ndash associations with disease phenotype treatment and outcome
topic dysbiosis
Crohn´s disease
ulcerative colitis
Proteobacteria
biologic therapy
Faecalibacterium prausnitzii
url https://www.dovepress.com/fecal-microbiota-profiles-in-treatment-naive-pediatric-inflammatory-bo-peer-reviewed-article-CEG
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