Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally - Validation Cohort

Background & Aims: Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric CD patients initiating therapy to identify microbial community features associated with CD and monitor changes after 8 weeks. Methods: Pediatric CD patients were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or from orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and again after 8 weeks. Treatment exposures included 5-ASAs, immunomodualtors, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). Results: A majority of subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in the CD group relative to healthy controls, while the remaining genera were decreased with antibiotic exposure. CD-associated genera were not differentially abundant following 8 weeks of therapy. Conclusions: Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance.