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Nature. 2019 May;569(7758):655-662. doi: 10.1038/s41586-019-1237-9. Epub 2019 May 29.

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Author information

1
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
3
Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
4
Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5
Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
6
Earth and Biological Sciences Directorate, Pacific Northwest National Lab, Richland, WA, USA.
7
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
8
Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
9
Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
10
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
11
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
12
Department of Pediatrics, Emory University, Atlanta, GA, USA.
13
Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, CA, USA.
14
Department of Odontology, Umeå University, Umeå, Sweden.
15
Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA.
16
Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
17
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
18
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA.
19
Department of Pathology & Immunology, Washington University, St. Louis, MO, USA.
20
Department of Pediatrics, MassGeneral Hospital for Children, Boston, MA, USA.
21
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
22
Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA.
23
Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. chuttenh@hsph.harvard.edu.
24
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. chuttenh@hsph.harvard.edu.

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.

PMID:
31142855
PMCID:
PMC6650278
[Available on 2019-11-29]
DOI:
10.1038/s41586-019-1237-9

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