Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota
Feng Wang,
Jess L. Kaplan,
Benjamin D. Gold,
Manoj K. Bhasin,
Naomi L. Ward,
Richard Kellermayer,
Barbara S. Kirschner,
Melvin B. Heyman,
Scot E. Dowd,
Stephen B. Cox,
Haluk Dogan,
Blaire Steven,
George D. Ferry,
Stanley A. Cohen,
Robert N. Baldassano,
Christopher J. Moran,
Elizabeth A. Garnett,
Lauren Drake,
Hasan H. Otu,
Leonid A. Mirny,
Towia A. Libermann,
Harland S. Winter,
Kirill S. Korolev
Affiliations
Feng Wang
Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA
Jess L. Kaplan
Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA
Benjamin D. Gold
Children’s Healthcare of Atlanta, LLC; GI Care for Kids, LLC; Atlanta, GA 30342, USA
Manoj K. Bhasin
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
Naomi L. Ward
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA
Richard Kellermayer
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Barbara S. Kirschner
Department of Pediatrics, University of Chicago Comer Children’s Hospital, Chicago, IL 60637, USA
Melvin B. Heyman
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA
Scot E. Dowd
Molecular Research MR DNA, Shallowater, TX 79363, USA
Stephen B. Cox
Molecular Research MR DNA, Shallowater, TX 79363, USA
Haluk Dogan
Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Blaire Steven
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA
George D. Ferry
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Stanley A. Cohen
Children’s Healthcare of Atlanta, LLC; GI Care for Kids, LLC; Atlanta, GA 30342, USA
Robert N. Baldassano
Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Christopher J. Moran
Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA
Elizabeth A. Garnett
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA
Lauren Drake
Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA
Hasan H. Otu
Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Leonid A. Mirny
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Towia A. Libermann
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
Harland S. Winter
Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA
Kirill S. Korolev
Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA
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.
