Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.
Bibliographical noteFunding Information:
We thank the patients who donated samples for this study, the health professionals who collected them, and the Crohn’s and Colitis Foundation of America for supporting the RISK cohort. We thank Douglas Wendel, Gail Ackermann, Tim Vigers, and Tim L. Tickle for their valuable input and helpful discussions. We thank participating clinicians Marla Dubinsky, Joshua Noe, Scott Snapper, Richard Kellermayer, Michael Kappleman, Anthony Otley, Mirian Pfefferkorn, Stanley Cohen, Stephen Guthery, Neal LeLeiko, Maria Oliva-Hemker, David Keljo, Dedrick Moulton, Barbara Kircshner, Ashish Patel, David Ziring, Jonathan Evans, Jonah Essers, Bruce Aronow, and MiOk Kim. Work was supported by grants from the Crohn’s and Colitis Foundation of America, The Leona M. and Harry B. Helmsley Charitable Trust, ARO grant W911NF-11-1-0473 (C.H.), and by NIH grants U54 DE023798, R01 HG005969 (C.H.), and R01 DK092405 (R.J.X., C.H., and D.G.).