P-234 Pediatric Crohn’s Disease Intrinsic Associations with the Subgingival Microbiota Revealed by a Prospective Longitudinal Cohort Study

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a dysbiotic intestinal microbiota. As oral manifestations are commonly seen in Crohn's disease (CD), we hypothesized that the oral microbiota may also be dysbiotic in patients with IBD. Our aim was to characterize the subgingival oral microbiota in a longitudinal cohort of pediatric patients with CD and healthy control (HC) subjects to determine whether there is an overall association with disease as well as with specific CD phenotypes. METHODS: CD cohort included new diagnoses whose treatment exposures included 5-ASAs, immunomodulators and steroids, and patients initiated on infliximab (IFX) therapy. Subgingival plaque samples were obtained longitudinally from both patients with CD and healthy controls at 2 time points, week 0 and week 8. In the IFX group, samples were obtained from patients with CD prior to IFX and at week 8 of therapy. Antibiotic exposure was evaluated in a subgroup analysis. Samples were analyzed by 16S rRNA gene sequencing. Disease activity was quantified using the Pediatric Crohn's Disease Activity Index (PCDAI) and by measuring fecal calprotectin (FC) levels. RESULTS: Subgingival samples were obtained from 35 patients with CD (28 on IFX and 7 new diagnoses) and 46 HC subjects. At time point 2, 80% and 87% of patients with CD demonstrated decrease in PCDAI and FC respectively, reflecting improvement in disease status. No subject had clinical evidence of gingivitis. The subgingival microbiota was different between CD and HC at the first timepoint (unweighted UniFrac, P < 0.03), where there was an increase in the relative abundance of Campylobacter genus in CD (weighted UniFrac, P < 0.001). A comparison of the microbiota between the 2 time points in patients with CD did not show any association with disease activity. Antibiotic exposure was associated with alterations in the subgingival microbiota (weighted and unweighted UniFrac, P < 0.001) with taxanomic alterations reminiscent of those previously described in patients treated for periodontitis. Finally, patients with CD who had extra-intestinal manifestations of joint pain were more similar to each other (beta dispersion, P < 0.02) and exhibited smaller alterations in their subgingival microbiota between the 2 time points (unweighted and weighted Unifrac, P < 0.03 and P < 0.004, respectively) compared to patients with CD without joint pain. CONCLUSIONS: In the absence of gingivitis, the structure of the subgingival microbiota in patients with CD is intrinsically different from that in HC subjects where the proportional abundance of Campylobacter is associated with disease. Within patients with CD, systemic influences associated with the development of a specific extra-intestinal manifestation may also impact upon the subgingival microbiota. Going forward, these data provide hypotheses for testing in future validation data sets. Surprisingly, there was no effect of disease activity, emphasizing the stability of these disease intrinsic associations. Nevertheless, extrinsic environmental factors, such as the use of antibiotics, result in predictable effects on the subgingival microbiota in CD.