title: The treatment-naive microbiome in new-onset Crohn's disease.
abstract: 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.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Gevers
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.affiliation: Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Vázquez-Baeza
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Van Treuren
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Boyu
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Schwager
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55108, USA.|BioTechnology Institute, University of Minnesota, St. Paul, MN 55108, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Knights
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Song
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Moran
authors.initials: M
authors.lastname: Yassour
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Xochitl C
authors.initials: XC
authors.lastname: Morgan
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Aleksandar D
authors.initials: AD
authors.lastname: Kostic
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Luo
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: McDonald
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Haberman
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walters
authors.affiliation: Children's Hospital of Buffalo, Buffalo, NY 14222, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Baker
authors.affiliation: Goryeb Children's Hospital, Morristown, NJ 07960, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.affiliation: Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Stephens
authors.affiliation: University of California, San Francisco, CA 94143, USA.
authors.forename: Melvin
authors.initials: M
authors.lastname: Heyman
authors.affiliation: North Shore Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Baldassano
authors.affiliation: Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.affiliation: Connecticut Children's Medical Center, Hartford, CT 06106, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sylvester
authors.affiliation: Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1 Canada.
authors.forename: David
authors.initials: D
authors.lastname: Mack
authors.affiliation: Nationwide Children's Hospital, Columbus, OH 43228, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kim
authors.affiliation: Nationwide Children's Hospital, Columbus, OH 43228, USA.
authors.forename: Wallace
authors.initials: W
authors.lastname: Crandall
authors.affiliation: Connecticut Children's Medical Center, Hartford, CT 06106, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hyams
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.|Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309, USA.|Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.|Howard Hughes Medical Institute, Boulder, CO 80309, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.|Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.|Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
mesh_terms: D000293:Adolescent; D001419:Bacteria / Q000145:classification* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000150:complications* / Q000382:microbiology*; D064806:Dysbiosis; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D054892:Metagenome; D064307:Microbiota