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Alterations in the gut microbiome of children with severe ulcerative colitis
Sonia Michail1, Matthew Durbin, Dan Turner
1Department of Pediatric Gastroenterology and Nutrition, University of Southern California, Los Angeles, California 90027, USA. Sonia.michail@hotmail.com
Insights
The gut microbiome is significantly less diverse in children with ulcerative colitis (UC). Non-response to steroid therapy in pediatric UC correlates with an even less diverse microbiome, suggesting a potential prognostic marker.
Area of Science:
- Microbiome research
- Pediatric gastroenterology
- Inflammatory Bowel Disease (IBD) studies
Background:
- The role of the gut microbiome in disease pathogenesis is recognized, but data on microbiome variability in pediatric ulcerative colitis (UC) are limited.
- This study focuses on characterizing the gut microbiome in hospitalized children with severe UC.
- The relationship between the gut microbiota and response to steroid therapy is investigated.
Purpose of the Study:
- To characterize the gut microbiome composition and diversity in children with severe UC.
- To compare the gut microbiome of children with UC to that of healthy controls.
- To determine if microbiome characteristics can predict response to steroid therapy in pediatric UC.
Main Methods:
- Prospective multicenter study involving fecal sample collection from 26 healthy controls and 27 hospitalized children with severe UC.
- DNA extraction, bacterial 16S rRNA gene amplification via PCR, and microarray hybridization were performed.
- Microbiome data were analyzed using GeneSpring GX 11.0, comparing UC patients with controls and steroid responders with nonresponders.
Main Results:
- Significant differences in bacterial signal strength and distribution were observed between UC patients and healthy controls across multiple taxonomic levels (Phylum to Phylospecies).
- Children with UC exhibited reduced microbial richness (phylospecies count) and lower Shannon Diversity Index compared to controls.
- Steroid nonresponders had a significantly less rich microbiome (fewer phylospecies) than steroid responders.
Conclusions:
- Gut microbiome richness, evenness, and biodiversity are significantly reduced in children with UC compared to healthy individuals.
- A less rich microbiome in children with UC is associated with non-response to steroid therapy.
- This study provides the first characterization of the gut microbiome in a large pediatric severe UC cohort and suggests microbiome changes may serve as a prognostic indicator.
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.
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