Bacterial Taxa and Functions Are Predictive of Sustained Remission following Exclusive Enteral Nutrition in Pediatric Crohn's Disease

Casey M.A. Jones, Jessica Connors, Katherine A. Dunn, Joseph P. Bielawski, André M. Comeau, Morgan G.I. Langille, Johan Van Limbergen

Résultat de recherche: Articleexamen par les pairs

40 Citations (Scopus)

Résumé

The gut microbiome is extensively involved in induction of remission in pediatric Crohn's disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks. Methods: A total of 139 fecal samples were obtained from 22 patients (8-15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn's Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels. Results: Microbial diversity did not change after EEN, but species richness was lower in low-FCP samples (<250 μg/g). An RF model using microbial abundances, species richness, and Paris disease classification was the best at classifying treatment response (area under the curve [AUC] = 0.9). KEGG Pathways also significantly classified treatment response with the addition of the same clinical data (AUC = 0.8). Top features of the RF model are consistent with previously identified IBD taxa, such as Ruminococcaceae and Ruminococcus gnavus. Conclusions: Our machine learning approach is able to distinguish SR and non-SR samples using baseline microbiome and clinical data.

Langue d'origineEnglish
Pages (de-à)1026-1037
Nombre de pages12
JournalInflammatory Bowel Diseases
Volume26
Numéro de publication7
DOI
Statut de publicationPublished - juin 18 2020

Note bibliographique

Funding Information:
Association Pfizer Young Investigator Pilot Research Award in Inflammatory Bowel Disease (2018), and a Weston Foundation Postbiotics grant (2019–2020). The MAREEN study was made possible through a NASPGHAN/CCFA Young Investigator award 2013–2015 for JVL. Conflicts of interest: JVL reports consulting, travel, and/or speaker fees and research support from AbbVie, Janssen, Nestlé Health Science, Novalac, Pfizer, Merck, P&G, GSK, Illumina, and Otsuka. Address correspondence to: Johan Van Limbergen MD, FRCPCH, PhD, Afdeling Kindergeneeskunde/Maag-, Darm-en Leverziekten, Locatie AMC, H7-228, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. E-mail: j.e.vanlimbergen@ amsterdamumc.nl. © 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com doi: 10.1093/ibd/izaa001 Published online 21 January 2020

Funding Information:
Research sponsored by the Crohn's & Colitis Foundation.

Funding Information:
From the *Department of Pharmacology, Dalhousie University, Halifax, Canada; †Department of Pediatrics, Dalhousie University, Halifax, Canada; ‡Department of Biology, Dalhousie University, Halifax, Canada; §Department of Mathematics & Statistics, Dalhousie University, Halifax, Canada; ¶Integrated Microbiome Resource (IMR), Dalhousie University, Halifax, Canada; ‖Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; **Department of Pediatrics, Division of Pediatric Gastroenterology & Nutrition, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands Supported by: JVL was supported by a Canadian Institutes of Health Research (CIHR)-Canadian Association of Gastroenterology-Crohn’s Colitis Canada New Investigator Award (2015–2019), a Canada Research Chair Tier 2 in Translational Microbiomics (2018–2019), and a Canadian Foundation of Innovation John R. Evans Leadership fund (awards #35235 and #36764), a Nova Scotia Health Research Foundation (NSHRF) establishment award (2015–2019), an IWK Health Centre Research Associateship, a Future Leaders in IBD project grant, a donation from the MacLeod family, a CIHR-SPOR-Chronic Diseases grant (Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects: the IMAGINE-SPOR chronic disease network), an American Gastroenterology

Publisher Copyright:
© 2020 Crohn's & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.

ASJC Scopus Subject Areas

  • Immunology and Allergy
  • Gastroenterology

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