Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.
BACKGROUND
Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric patients with CD initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy.


METHODS
Pediatric patients with CD were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodulators, 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
Most 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 CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared with healthy controls after 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.
*Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; †Department of Microbiology; and ‡Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Judith
J
Kelsen
Kyle
K
Bittinger
Helen
H
Pauly-Hubbard
Leah
L
Posivak
Stephanie
S
Grunberg
Robert
R
Baldassano
James D
JD
Lewis
Gary D
GD
Wu
Frederic D
FD
Bushman
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002206:Capnocytophaga; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005881:Gingiva / Q000382:microbiology* / Q000473:pathology; D005882:Gingival Diseases / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000069285:Infliximab / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D064307:Microbiota / Q000187:drug effects* / Q000235:genetics; D012336:RNA, Ribosomal, 16S; D013256:Steroids / Q000627:therapeutic use; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D007155:Immunologic Factors; D012336:RNA, Ribosomal, 16S; D013256:Steroids; D019804:Mesalamine; D000069285:Infliximab