Distinct Microbiotas are Associated with Ileum-Restricted and Colon-Involving Crohn's Disease.

Abstract

The etiology of inflammatory bowel disease is believed to involve a shift in the microbiota toward more proinflammatory species. Crohn's disease (CD) usually manifests as one of three phenotypes, involving inflammation of the terminal ileum, the colon, or both. However, what determines the particular phenotype and the level of disease activity remains unknown. In this study, we aim to characterize the intestinal microbiota associated with different CD phenotypes. DNA was extracted from biopsies of 31 patients with ileal, ileocolic, or colon-restricted CD, and also from 5 non-inflammatory bowel disease control subjects, and analyzed by 16S rRNA gene amplicon pyrosequencing. Data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analyzed using linear discriminant analysis with effect size estimation and PICRUSt algorithms. Two additional recently published cohorts were also analyzed in this study. Highly significant separation was observed between bacterial composition of ileal CD compared with CD with colonic involvement (genus level Bray-Curtis P = 0.005, R = 20%). This separation was unaffected by the biopsy's location or its inflammatory state, or by the patients' condition (remission or relapse). Faecalibacterium was strongly reduced in ileal CD compared with CD with colonic involvement, whereas Enterobacteriaceae were more abundant in the former. Fusobacterium relative abundance was strongly correlated with disease activity in patients with ileal-involving, but not in colon-involving, CD. Ileal and colon-involving CD sustain distinct microbiotas, suggesting that different mechanisms underlie the two major manifestations of CD. The potential contribution of Fusobacterium to inflammation in ileal CD should be further investigated.