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 multi-center study. DNA extraction, PCR amplification of bacterial 16S rRNA, and microarray hybridization were performed. Results were analyzed in Genespring GX 11.0 comparing healthy controls to children with UC, and steroid responsive (n=17) to non-responsive 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). Steroids non-responders harbored less 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 to 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 ulcerative colitis and describes changes in the gut microbiome as a potential prognostic feature.
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