16S rRNA gene stool microbiome pediatric patients with ulcerative colitis Targeted Locus (Loci). human gut metagenome

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 that composition and function of the intestinal microbiome of patients with ulcerative colitis (UC), a subtype of IBD, is altered. 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 significant increases in the phylum Actinobacteria and class Gammaproteobacteria 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 metabolic pathway differences between the groups. To determine if microbial factors may be associated with clinical outcomes, we retrospectively assessed the clinical course of the UC patients. By using principal components analysis of unweighted UniFrac distances we found a significant separation (p=0.013) between early responders and non-responders to conventional treatments. Our metagenomic observations and their association with differential clinical outcomes in pediatric patients with UC further the notion that the microbiota may be a significant contributor to disease onset and modulation in this disease group.