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Variation of Gut Mucosal Microbiome With Anti-Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease

Kansal, Shivani*,†,‡; Catto-Smith, Anthony G.‡,§; Boniface, Karen; Thomas, Sarah; Cameron, Donald J.*; Oliver, Mark*; Alex, George*; Kirkwood, Carl D.†,¶; Wagner, Josef‡,||

Journal of Pediatric Gastroenterology and Nutrition: December 2019 - Volume 69 - Issue 6 - p 696–703
doi: 10.1097/MPG.0000000000002461
Original Article: Gastroenterology: Inflammatory Bowel Disease
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Objectives: Crohn disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. Approximately 30% to 60% of patients with CD have anti-Saccharomyces cerevisiae antibody (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype.

Methods: Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity, and clinical characteristics.

Results: ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease, and long-term risk of surgery. Microbial alpha and beta diversity were similar in patients with CD with or without ASCA, but significantly less when compared to noninflammatory bowel disease controls. Microbial richness was similar across all 3 groups. Fourteen bacterial species were associated with ASCA-positive patients with CD and 14 species with ASCA-negative patients (P < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterocolitica 61 remained significantly associated with CD ASCA positivity (P = 0.0178), whereas Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (P = 0.0178 and 0.0342).

Conclusion: ASCA-positive and ASCA-negative patients with CD have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.

*Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital

Enteric Virus Group, Murdoch Children's Research Institute

Department of Pediatrics, University of Melbourne, Parkville, Victoria

§Department of Gastroenterology, Hepatology and Liver Transplant, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia

Enteric and Diarrheal Diseases, Global Health, Bill and Melinda Gates Foundation, Seattle, WA

||Wellcome Trust, Sanger Institute, Cambridge, UK.

Address correspondence and reprint requests to Dr Shivani Kansal, Department of Gastroenterology, Royal Children's Hospital, Flemington Rd, Parkville, Melbourne, Australia 3052 (e-mail: shivani.kansal@mcri.edu.au).

Received 25 October, 2018

Accepted 25 July, 2019

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

This study was supported by grants from the Australian National and Medical Research Institute and by the Victoria State Scientific Infrastructure Scheme. Carl Kirkwood was supported by an NHMRC CDA Senior Research Fellowship. (607382).

All study participants, or their legal guardian, provided informed written consent prior to study enrolment.

The study was performed after ethics approval from the RCH Human Research Ethics Committee (HREC30002A).

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,