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Alterations in the gut microbiome of children with severe ulcerative colitis

Michail, Sonia MD1; Durbin, Matthew MD1; Turner, Dan MD, PhD2; Griffiths, Anne M. MD3; Mack, David R. MD4; Hyams, Jeffrey MD6; Leleiko, Neal MD, PhD5; Kenche, Harshavardhan MS1; Stolfi, Adrienne MSPH1; Wine, Eytan MD, PhD7

doi: 10.1002/ibd.22860
Original Article: Original Clinical Articles

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. (Inflamm Bowel Dis 2012)

1Department of Pediatric Gastroenterology and Nutrition, University of Southern California, Los Angeles, California, USA

2Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel

3Hospital for Sick Children, Toronto, Ontario, Canada

4Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada

5Connecticut Children's Med Center, Hartford, Connecticut, USA

6Hasbro Children's Hospital, Providence, Rhode Island, USA

7Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

Reprints: Sonia Michail, MD, AGAF, FAAP, CPE, University of Southern California and CHLA, 4650 Sunset Blvd., MS#78, Los Angeles CA 90027 (e-mail: Sonia.michail@hotmail.com) or Eytan Wine, MD, PhD, Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, 11405 – 87 Ave., Edmonton, AB T6G 1C9, Canada (e-mail: wine@ualberta.ca).

Received for publication 15 November 2011; Accepted 28 November 2011

Supported by the National Institutes of Health (NIH), Grant number: NCCAM AT003400; and the Children's Medical Center Research Foundation. Partial funding was obtained from Schering-Plough, Canada, which allowed patient recruitment and stool collection. E.W. is an Alberta Innovates Health Solutions (AIHS) Clinical Investigator. Infrastructure in E.W.'s laboratory is funded by the Centre for Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR) at the University of Alberta and the Alberta Inflammatory Bowel Disease Consortium, which is supported by an AIHS Interdisciplinary Team Grant.

© Crohn's & Colitis Foundation of America, Inc.
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