title: Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Harvard/MIT Health Science and Technology Institute, Cambridge, Massachusetts, United States of America.
authors: Eliseo
authors: E
authors: Papa
authors: Michael
authors: M
authors: Docktor
authors: Christopher
authors: C
authors: Smillie
authors: Sarah
authors: S
authors: Weber
authors: Sarah P
authors: SP
authors: Preheim
authors: Dirk
authors: D
authors: Gevers
authors: Georgia
authors: G
authors: Giannoukos
authors: Dawn
authors: D
authors: Ciulla
authors: Diana
authors: D
authors: Tabbaa
authors: Jay
authors: J
authors: Ingram
authors: David B
authors: DB
authors: Schauer
authors: Doyle V
authors: DV
authors: Ward
authors: Joshua R
authors: JR
authors: Korzenik
authors: Ramnik J
authors: RJ
authors: Xavier
authors: Athos
authors: A
authors: Bousvaros
authors: Eric J
authors: EJ
authors: Alm
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D044822:Biodiversity; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000175:diagnosis / Q000382:microbiology / Q000473:pathology; D003710:Demography; D003937:Diagnosis, Differential; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000473:pathology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D054892:Metagenome / Q000235:genetics; D012074:Remission Induction; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D012984:Software; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D039841:Leukocyte L1 Antigen Complex