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

Journal Article · · Nature (London)
 [1];  [2];  [3];  [4];  [5];  [5];  [3];  [6];  [7];  [8];  [9];  [3];  [10];  [9];  [5];  [11];  [12];  [7];  [5];  [13] more »;  [7];  [9];  [14];  [10];  [8];  [9];  [15];  [8];  [10];  [13];  [12];  [6];  [16];  [17];  [5];  [18];  [5];  [19];  [7] « less
  1. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Harvard T.H. Chan School of Public Health, Boston, MA (United States)
  2. Harvard T.H. Chan School of Public Health, Boston, MA (United States)
  3. Massachusetts General Hospital, Boston, MA (United States)
  4. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
  5. Broad Institute of MIT and Harvard, Cambridge, MA (United States)
  6. Baylor College of Medicine, Houston, TX (United States)
  7. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Harvard T. H. Chan School of Public Health, Boston, MA (United States)
  8. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  9. Univ. of California Los Angeles, Los Angeles, CA (United States)
  10. Univ. of California San Diego, La Jolla, CA (United States)
  11. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (United States)
  12. Cedars-Sinai Medical Center, Los Angeles, CA (United States)
  13. Emory Univ., Atlanta, GA (United States)
  14. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Umea Univ., Umea (Sweden)
  15. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (United States); Univ. of Cincinnati College of Medicine, Cincinnati, OH (United States)
  16. Washington Univ., St. Louis, MO (United States)
  17. MassGeneral Hospital for Children, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)
  18. Harvard T. H. Chan School of Public Health, Boston, MA (United States)
  19. Broad Institute of MIT and Harvard, Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

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. Lastly, 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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Contributing Organization:
IBDMDB Investigators
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
1573018
Report Number(s):
PNNL-SA-132723
Journal Information:
Nature (London), Vol. 569, Issue 7758; ISSN 0028-0836
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 1200 works
Citation information provided by
Web of Science

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