The Treatment-Naive Microbiome in New-Onset Crohn’s Disease

• DOI: 10.1016/j.chom.2014.02.005
• Publication Date: 2014-03-15T15:15:33Z
• Authors: Dirk Gevers; Subra Kugathasan; Lee A. Denson; Yoshiki Vázquez-B...; Will Van Treuren; Boyu Ren; Emma Schwager; Dan Knights; Se Jin Song; Moran Yassour; Xochitl C. Morgan; Aleksandar D. Kostic; Chengwei Luo; Antonio González; Daniel McDonald; Yael Haberman; Thomas Walters; Susan Baker; Joel Rosh; Michael Stephens; Melvin Heyman; James Markowitz; Robert Baldassano; Anne Griffiths; Francisco Sylvester; David Mack; Sandra Kim; Wallace Crandall; Jeffrey Hyams; Curtis Huttenhower; Rob Knight; Ramnik J. Xavier
• Keywords: Cancer Research; Adolescent; Immunology; Crohn's Disease; Autoimmune Disease; Microbiology; Oral and gastrointestinal; Cohort Studies; Crohn Disease; Clinical Research; Immunology and Microbiology(all); 2.1 Biological and endogenous factors; Humans; Aetiology; Preschool; Child; Molecular Biology; Pediatric; screening and diagnosis; Bacteria; Prevention; Microbiota; Inflammatory Bowel Disease; 4.1 Discovery and preclinical testing of markers and technologies; 3. Good health; Gastrointestinal Tract; Detection; Medical Microbiology; Child, Preschool; Dysbiosis; Metagenome; Digestive Diseases

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.