Microbiota separation and C-reactive protein elevation in treatment-naïve pediatric granulomatous Crohn disease.
OBJECTIVE
In patients with inflammatory bowel diseases (IBDs), the presence of noncaseating mucosal granuloma is sufficient for diagnosing Crohn disease (CD) and may represent a specific immune response or microbial-host interaction. The cause of granulomas in CD is unknown and their association with the intestinal microbiota has not been addressed with high-throughput methodologies.


METHODS
The mucosal microbiota from 3 different pediatric centers was studied with 454 pyrosequencing of the bacterial 16S rRNA gene and the fungal small subunit (SSU) ribosomal region in transverse colonic biopsy specimens from 26 controls and 15 treatment-naïve pediatric CD cases. Mycobacterium avium subspecies paratuberculosis (MAP) was tested with real-time polymerase chain reaction. The correlation of granulomatous inflammation with C-reactive protein was expanded to 86 treatment-naïve CD cases.


RESULTS
The CD microbiota separated from controls by distance-based redundancy analysis (P = 0.035). Mucosal granulomata found in any portion of the intestinal tract associated with an augmented colonic bacterial microbiota divergence (P = 0.013). The granuloma-based microbiota separation persisted even when research center bias was eliminated (P = 0.04). Decreased Roseburia and Ruminococcus in granulomatous CD were important in this separation; however, principal coordinates analysis did not reveal partitioning of the groups. CRP levels >1 mg/dL predicted the presence of mucosal granulomata (odds ratio 28 [6-134.32]; 73% sensitivity, 91% specificity).


CONCLUSIONS
Granulomatous CD associates with microbiota separation and C-reactive protein elevation in treatment-naïve children; however, overall dysbiosis in pediatric CD appears rather limited. Geographical/center bias should be accounted for in future multicenter microbiota studies.
Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Texas Children's Hospital, Houston, USA. kellerma@bcm.edu
Richard
R
Kellermayer
Sabina A V
SA
Mir
Dorottya
D
Nagy-Szakal
Stephen B
SB
Cox
Scot E
SE
Dowd
Jess L
JL
Kaplan
Yan
Y
Sun
Sahna
S
Reddy
Jiri
J
Bronsky
Harland S
HS
Winter
D000293:Adolescent; D015373:Bacterial Typing Techniques; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D044684:Colon, Transverse / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000150:complications / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology; D006099:Granuloma / Q000209:etiology / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000235:genetics*; D016017:Odds Ratio; D012336:RNA, Ribosomal, 16S; D054679:Ribosome Subunits, Small
D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D002097:C-Reactive Protein