Journal Article

Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease

Smillie, Christopher, Ward, Doyle V., Gevers, Dirk, Bousvaros, Athos, Papa, Eliseo, Schauer, David B., Alm, Eric J., Giannoukos, Georgia, Docktor, Michael, Korzenik, Joshua R., Ciulla, Dawn, Xavier, Ramnik J., Preheim, Sarah P., Tabbaa, Diana, Ingram, Jay, Weber, Sarah

2012

Overview

Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children's Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn's disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Adults / Analytical methods / Anti-Bacterial Agents - therapeutic use / Biodiversity / Bioengineering / Bioinformatics / Biology / Biopsy / Blood tests / Child / Child health / Child, Preschool / Children / Clinical trials / Cohort Studies / Colitis, Ulcerative - diagnosis / Colitis, Ulcerative - microbiology / Colitis, Ulcerative - pathology / Colon / Colonoscopy / Crohn Disease - diagnosis / Crohn Disease - microbiology / Crohn Disease - pathology / Crohn's disease / Data analysis / Demography / Diagnosis / Diagnosis, Differential / Diagnostic software / Diagnostic systems / Ecological monitoring / Ecology / Endoscopes / Endoscopy / Engineering / Environmental engineering / Feces - microbiology / Female / Gastroenterology / Gastrointestinal diseases / Gastrointestinal Tract - microbiology / Gastrointestinal Tract - pathology / Gastrointestinal tract diseases / Genomes / Hospitals / Humans / Identification methods / Inflammatory bowel disease / Inflammatory bowel diseases / Inflammatory Bowel Diseases - classification / Inflammatory Bowel Diseases - diagnosis / Inflammatory Bowel Diseases - drug therapy / Inflammatory Bowel Diseases - microbiology / Intestine / Leukocyte L1 Antigen Complex - metabolism / Male / Medical diagnosis / Medicine / Metagenome - genetics / Microbiota / Microbiota (Symbiotic organisms) / Microorganisms / Patients / Pediatrics / Remission Induction / Reproducibility of Results / RNA / rRNA 16S / Sensitivity / Severity of Illness Index / Slime / Software / Studies / Surveys / Taxa / Taxonomy / Ulcerative colitis / Young Adult / Young adults