Sa1164 Exclusive Enteral Nutrition Optimizes Growth Outcomes Versus Corticosteroid Therapy for Pediatric Crohn's Disease

Background: The pathogenesis of IBD involves a genetically-determined dysregulation of mucosal immunity in response to environmental factors such as the gut microbiota. Multiple studies have shown the bacterial microbiota to be dysbiotic with an increase in Proteobacteria and a decrease in taxonomic richness. Serologic evidence in patients with IBD as well as mechanistic studies in murine models suggests that gut fungi, collectively referred to as the mycobiome, may also play a role in the pathogenesis of IBD. In this study, we utilized recently described analytic platforms to compare members of the gut microbiota from all three domains of life, Bacteria, Archaea, and Eukaryota in patients with IBD to healthy human subjects. Methods: A single stool sample was collected from pediatric patients with either Crohn's disease (CD) or ulcerative colitis (UC). DNA was extracted using the PSP DNA extraction kit. Pyrosequencing was carried out using barcoded primers. Domainspecific16S rRNA gene primers were used to analyze bacteria and archaea and ITS primers were used to analyze fungi. Sequences obtained were decoded using the QIIME pipeline. The results were compared to a cohort of pediatric control subjects from a previously published study (Hoffmann C. et al. PloS ONE 2013 8(6):e66019). In the IBD cohort, clinical records were obtained and disease activity was measured by the Pediatric Crohn Disease Activity Index (PCDAI). Results: Stool samples were collected from 32 pediatric IBD patients. The majority of these patients (81%) had CD. Four patients had UC and 2 patients had indeterminate colitis. Similar to previously published studies, IBD patients demonstrated decreased bacterial diversity. Although ITS sequencing showed that fecal DNA from patients with IBD and healthy subjects had a similar number of fungal reads, the two groups clustered separately on a principal coordinate analysis (Figure 1) suggesting differences in the mycobiome. Both Pichia jadinii and Candida parapsilosis were significantly more abundant in IBD patients (p = 0.0034 and P=0.00038, respectively). By contrast, an unclassified Candida taxon (OTU EU490138) was more abundant in healthy subjects (p=0.0025). There were no statistically significant differences in the archaeal microbiota. Within the CD patients, age, race, current medications, and PCDAI were not correlated with bacterial microbiota composition. Conclusions: Pediatric IBD is associated with an alteration in the gut mycobiota with increased proportions of both Pichia jadinii and Candida parapsilosis. Although some species within the Pichia genus are known to be pathogenic in immunocompromised hosts, additional studies will be needed to determine whether or not they play a role in the pathogenesis of IBD in humans.