title: Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota.
abstract: The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis.
authors.affiliation: Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jess L
authors.initials: JL
authors.lastname: Kaplan
authors.affiliation: Children's Healthcare of Atlanta, LLC; GI Care for Kids, LLC; Atlanta, GA 30342, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Gold
authors.affiliation: BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center and Department of Medicine, Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Bhasin
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Ward
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.affiliation: Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, IL 60637, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Kirschner
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Melvin B
authors.initials: MB
authors.lastname: Heyman
authors.affiliation: Molecular Research MR DNA, Shallowater, TX 79363, USA.
authors.forename: Scot E
authors.initials: SE
authors.lastname: Dowd
authors.affiliation: Molecular Research MR DNA, Shallowater, TX 79363, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Cox
authors.affiliation: Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Haluk
authors.initials: H
authors.lastname: Dogan
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Blaire
authors.initials: B
authors.lastname: Steven
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Ferry
authors.affiliation: Children's Healthcare of Atlanta, LLC; GI Care for Kids, LLC; Atlanta, GA 30342, USA.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Cohen
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moran
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Garnett
authors.affiliation: Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Drake
authors.affiliation: Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Hasan H
authors.initials: HH
authors.lastname: Otu
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Mirny
authors.affiliation: BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center and Department of Medicine, Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Towia A
authors.initials: TA
authors.lastname: Libermann
authors.affiliation: Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA. Electronic address: hwinter@partners.org.
authors.forename: Harland S
authors.initials: HS
authors.lastname: Winter
authors.affiliation: Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA; Department of Physics, Boston University, Boston, MA 02215, USA. Electronic address: korolev@bu.edu.
authors.forename: Kirill S
authors.initials: KS
authors.lastname: Korolev
mesh_terms: D000293:Adolescent; D015373:Bacterial Typing Techniques / Q000379:methods*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000150:complications / Q000175:diagnosis / Q000382:microbiology*; D064806:Dysbiosis / Q000150:complications / Q000175:diagnosis / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D007223:Infant; D064307:Microbiota