title: Alterations in the gut microbiome of children with severe ulcerative colitis.
abstract: BACKGROUND
  Although the role of microbes in disease pathogenesis is well established, data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis (UC) are lacking. This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy.
  
  
  METHODS
  Fecal samples were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospective multicenter study. DNA extraction, polymerase chain reaction (PCR) amplification of bacterial 16S rRNA, and microarray hybridization were performed. Results were analyzed in GeneSpring GX 11.0 comparing healthy controls with children with UC, and steroid responsive (n = 17) with nonresponsive patients (n = 10).
  
  
  RESULTS
  Bacterial signal strength and distribution showed differences between UC and healthy controls (adjusted P < 0.05) for Phylum, Class, Order, Family, Genus, and Phylospecies levels with reduction in Clostridia and an increase in Gamma-proteobacteria. The number of microbial phylospecies was reduced in UC (266 ± 69) vs. controls (758 ± 3, P < 0.001), as was the Shannon Diversity Index (6.1 ± 0.23 vs. 6.49 ± 0.04, respectively; P < 0.0001). Steroid nonresponders harbored fewer phylospecies than responders (142 ± 49 vs. 338 ± 62, P = 0.013).
  
  
  CONCLUSIONS
  Richness, evenness, and biodiversity of the gut microbiome were remarkably reduced in children with UC compared with healthy controls. Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders. This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe UC and describes changes in the gut microbiome as a potential prognostic feature.
authors.affiliation: Department of Pediatric Gastroenterology and Nutrition, University of Southern California, Los Angeles, California 90027, USA. Sonia.michail@hotmail.com
authors.forename: Sonia
authors.initials: S
authors.lastname: Michail
authors.forename: Matthew
authors.initials: M
authors.lastname: Durbin
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
authors.forename: David R
authors.initials: DR
authors.lastname: Mack
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hyams
authors.forename: Neal
authors.initials: N
authors.lastname: Leleiko
authors.forename: Harshavardhan
authors.initials: H
authors.lastname: Kenche
authors.forename: Adrienne
authors.initials: A
authors.lastname: Stolfi
authors.forename: Eytan
authors.initials: E
authors.lastname: Wine
mesh_terms: D000293:Adolescent; D001419:Bacteria / Q000472:pathogenicity*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000235:genetics / Q000382:microbiology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004269:DNA, Bacterial / Q000235:genetics; D005243:Feces / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020869:Gene Expression Profiling; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D054892:Metagenome; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial