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.

Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Figures

Figure 1. Microbial biodiversity is reduced in children with severe ulcerative colitis

Mean (±SD) Shannon index of biodiversity in healthy controls (Healthy) and patients with severe ulcerative colitis (UC). * p

Figure 2. Phylum level changes in severe ulcerative colitis

Percent of raw signals for each of the 9 measured phyla are presented. Patients with severe ulcerative colitis had relative reductions in Firmicutes, Verrucomicrobiae, and Lentisphaerae and increases in Proteobacteria, Fusobacteria, and Spirochaetes. * corrected p

Figure 3. Reduced microbial intensities in pediatric ulcerative colitis

Profile plot representation of normalized signal intensities of each of the phylospecies in children with ulcerative colitis (UC) vs. healthy controls (Healthy). Each line represents one of the 852 phylospecies. The figure demonstrates a dramatic decrease in the signal intensity for the majority of the phylospecies.

Figure 4. Diminished microbial richness correlates with ulcerative colitis and lack of response to steroids

Number of species detected in fecal samples of healthy children (Healthy) and children with severe ulcerative colitis showing statistically significant difference (** p