Variation of Gut Mucosal Microbiome with ASCA Status in Pediatric Crohn's Disease.

Abstract

OBJECTIVES Crohn's Disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. About 30-60% of CD patients have antibodies to Saccharomyces cerevisiae (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 CD patients with or without ASCA, but significantly less when compared to non-IBD controls. Microbial richness was similar across all three groups. Fourteen bacterial species were associated with ASCA positive CD patients and 14 species with ASCA negative patients (p < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterolitica 61 remained significantly associated with CD ASCA positivity (p = 0.0178), while Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (p = 0.0178 and 0.0342). CONCLUSION ASCA positive and ASCA negative CD patients have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.