Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis

ABSTRACT

Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory disorders characterized by a complex disruption of the physiologic interaction between the host immune system and intestinal microbes precipitated by environmental factors. Numerous observations indicate the altered composition and function of the intestinal microbiome of patients with ulcerative colitis (UC), a subtype of IBD. The accuracy of these results may be limited by confounding factors, such as concurrent medication use. To address these limitations, we examined the colonic mucosal microbiome of pediatric patients with UC prior to initiating treatment. Based on bacterial 16S rRNA gene sequencing, we identified a significant decrease in the phylum Verrucomicrobia in patients with UC. At the genus level, we observed a significant decrease in the short chain fatty acid producer Roseburia. Despite these compositional changes, we did not identify inferred gene content differences between the UC and control groups. To determine if microbial taxa may be associated with clinical outcomes, we retrospectively assessed the clinical course of the UC patients. Despite similar metrics of OTU richness and diversity, multiple OTU differences were observed between patients who responded to therapy and those who did not. Our observations regarding the mucosal microbiome and the associations with differential clinical outcomes support the contributions of gut microbes to disease onset and modulation.