Microbiota Separation and C‐reactive Protein Elevation in Treatment‐naïve Pediatric Granulomatous Crohn Disease

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 55; no. 3; pp. 243 - 250
• Main Authors: Kellermayer, Richard, Mir, Sabina A.V., Nagy‐Szakal, Dorottya, Cox, Stephen B., Dowd, Scot E., Kaplan, Jess L., Sun, Yan, Reddy, Sahna, Bronsky, Jiri, Winter, Harland S.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Copyright by ESPGHAN and NASPGHAN 01.09.2012; Lippincott Williams & Wilkins
• Subjects: Adolescent; Bacterial Typing Techniques; Biological and medical sciences; Biopsy; C-Reactive Protein - metabolism; Case-Control Studies; Child; Colon, Transverse - microbiology; Colon, Transverse - pathology; Crohn disease; Crohn Disease - complications; Crohn Disease - microbiology; Crohn Disease - pathology; DNA, Bacterial; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; fungi; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Tract - microbiology; Gastrointestinal Tract - pathology; granuloma; Granuloma - etiology; Granuloma - microbiology; Humans; Inflammation - microbiology; inflammatory bowel disease; Intestinal Mucosa - microbiology; Male; Medical sciences; Metagenome - genetics; microbiota; Odds Ratio; Other diseases. Semiology; Ribosome Subunits, Small; RNA, Ribosomal, 16S; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; microbiota; Granuloma; Pediatrics; Granulomatosis; Metabolic diseases; Inflammatory disease; Inflammatory bowel disease; Crohn disease; Treatment; fungi; Gastroenterology; Digestive diseases; Intestinal disease; C reactive protein; Child; Ulcerative colitis
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/MPG.0b013e3182617c16

ABSTRACT Objectives: 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.