Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-05-29

AUTHORS

Jason Lloyd-Price, Cesar Arze, Ashwin N. Ananthakrishnan, Melanie Schirmer, Julian Avila-Pacheco, Tiffany W. Poon, Elizabeth Andrews, Nadim J. Ajami, Kevin S. Bonham, Colin J. Brislawn, David Casero, Holly Courtney, Antonio Gonzalez, Thomas G. Graeber, A. Brantley Hall, Kathleen Lake, Carol J. Landers, Himel Mallick, Damian R. Plichta, Mahadev Prasad, Gholamali Rahnavard, Jenny Sauk, Dmitry Shungin, Yoshiki Vázquez-Baeza, Richard A. White, Jonathan Braun, Lee A. Denson, Janet K. Jansson, Rob Knight, Subra Kugathasan, Dermot P. B. McGovern, Joseph F. Petrosino, Thaddeus S. Stappenbeck, Harland S. Winter, Clary B. Clish, Eric A. Franzosa, Hera Vlamakis, Ramnik J. Xavier, Curtis Huttenhower

ABSTRACT

Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, affect several million individuals worldwide. Crohn’s disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study’s infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi’omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases. More... »

PAGES

655-662

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  • Journal

    TITLE

    Nature

    ISSUE

    7758

    VOLUME

    569

    Author Affiliations

  • Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
  • Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
  • Earth and Biological Sciences Directorate, Pacific Northwest National Lab, Richland, WA, USA
  • Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
  • Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
  • Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA
  • Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
  • F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • Department of Pediatrics, Emory University, Atlanta, GA, USA
  • Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA, USA
  • Department of Odontology, Umeå University, Umeå, Sweden
  • Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
  • Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
  • Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
  • Department of Pathology & Immunology, Washington University, St. Louis, MO, USA
  • Department of Pediatrics, Harvard Medical School, Boston, MA, USA
  • Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Clinical Trials linked to this publication

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-019-1237-9

    DOI

    http://dx.doi.org/10.1038/s41586-019-1237-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1115981538

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31142855


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