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.
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: C Manichanh; L Rigottier-Gois; E Bonnaud; K Gloux; E Pelletier; L Frangeul; R Nalin; C Jarrin; P Chardon; P Marteau; J Roca; J Dore Journal: Gut Date: 2005-09-27 Impact factor: 23.059
Authors: M P Conte; S Schippa; I Zamboni; M Penta; F Chiarini; L Seganti; J Osborn; P Falconieri; O Borrelli; S Cucchiara Journal: Gut Date: 2006-04-28 Impact factor: 23.059
Authors: Steven R Gill; Mihai Pop; Robert T Deboy; Paul B Eckburg; Peter J Turnbaugh; Buck S Samuel; Jeffrey I Gordon; David A Relman; Claire M Fraser-Liggett; Karen E Nelson Journal: Science Date: 2006-06-02 Impact factor: 47.728
Authors: Claudia Lupp; Marilyn L Robertson; Mark E Wickham; Inna Sekirov; Olivia L Champion; Erin C Gaynor; B Brett Finlay Journal: Cell Host Microbe Date: 2007-08-16 Impact factor: 21.023
Authors: Dan Turner; Anthony R Otley; David Mack; Jeffrey Hyams; J de Bruijne; Krista Uusoue; Thomas D Walters; Mary Zachos; Petar Mamula; Dorcas E Beaton; A Hillary Steinhart; Anne M Griffiths Journal: Gastroenterology Date: 2007-05-21 Impact factor: 22.682
Authors: Daniel N Frank; Allison L St Amand; Robert A Feldman; Edgar C Boedeker; Noam Harpaz; Norman R Pace Journal: Proc Natl Acad Sci U S A Date: 2007-08-15 Impact factor: 11.205