Dysbiosis, inflammation, and response to treatment: A longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease

• Type of Material: Article
• Authors: Kelly A. Shaw, Emory University; Madeline Bertha, Children's Healthcare of Atlanta; Tatyana Hofmekler, Emory University; Pankaj Chopra, Children's Healthcare of Atlanta; Tommi Vatanen, Broad Institute of MIT and Harvard; Abhiram Srivatsa, Children's Healthcare of Atlanta; Jarod Prince, Children's Healthcare of Atlanta; Archana Kumar, Children's Healthcare of Atlanta; Cary Sauer, Emory University; Michael Zwick, Emory University; Glen Satten, Emory University; Aleksandar D. Kostic, Broad Institute of MIT and Harvard; Jennifer Mulle, Emory University; Ramnik J. Xavier, Broad Institute of MIT and Harvard; Subramaniam Kugathasan, Emory University
• Language: English
• Date: 2016-07-13
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Author(s).
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13073-016-0331-y
• Title of Journal or Parent Work: Genome Medicine
• ISSN: 1756-994X
• Volume: 8
• Issue: 1
• Start Page: 75
• End Page: 75
• Grant/Funding Information: The Marcus Foundation (to SK) primarily supported this work, with further support from DK087694 (SK) and DK098231 (SK).; KAS received support from BWF training grant ID 1008188 and NIH NRSA F31DK107229.
• Keywords: Microbiome; Dysbiosis; Crohn’s disease; Inflammatory bowel disease
• Research Categories: Health Sciences, Epidemiology; Biology, Molecular; Biology, Genetics

Abstract

Background: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome. Methods: We performed a prospective cohort study of 19 treatment-naïve pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples. Results: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status. Conclusions: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment.