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Title: Murine colitis reveals a disease-associated bacteriophage community

Abstract

The dysregulation of intestinal microbial communities is associated with inflammatory bowel diseases (IBD). Studies aimed at understanding the contribution of the microbiota to inflammatory diseases have primarily focused on bacteria, yet the intestine harbours a viral component dominated by prokaryotic viruses known as bacteriophages (phages). Phage numbers are elevated at the intestinal mucosal surface and phages increase in abundance during IBD, suggesting that phages play an unidentified role in IBD. We used a sequence-independent approach for the selection of viral contigs and then applied quantitative metagenomics to study intestinal phages in a mouse model of colitis. We discovered that during colitis the intestinal phage population is altered and transitions from an ordered state to a stochastic dysbiosis. We identified phages specific to pathobiotic hosts associated with intestinal disease, whose abundances are altered during colitis. Additionally, phage populations in healthy and diseased mice overlapped with phages from healthy humans and humans with IBD. Our findings indicate that intestinal phage communities are altered during inflammatory disease, establishing a platform for investigating phage involvement in IBD.

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3];  [4];  [3]; ORCiD logo [4];  [4];  [3]; ORCiD logo [4]
  1. Univ. of Colorado School of Medicine, Aurora, CO (United States)
  2. North Carolina State Univ., Raleigh, NC (United States)
  3. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
  4. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1543763
Grant/Contract Number:  
[AC02-05CH11231]
Resource Type:
Accepted Manuscript
Journal Name:
Nature Microbiology
Additional Journal Information:
[ Journal Volume: 3; Journal Issue: 9]; Journal ID: ISSN 2058-5276
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Microbiology

Citation Formats

Duerkop, Breck A., Kleiner, Manuel, Paez-Espino, David, Zhu, Wenhan, Bushnell, Brian, Hassell, Brian, Winter, Sebastian E., Kyrpides, Nikos C., and Hooper, Lora V. Murine colitis reveals a disease-associated bacteriophage community. United States: N. p., 2018. Web. doi:10.1038/s41564-018-0210-y.
Duerkop, Breck A., Kleiner, Manuel, Paez-Espino, David, Zhu, Wenhan, Bushnell, Brian, Hassell, Brian, Winter, Sebastian E., Kyrpides, Nikos C., & Hooper, Lora V. Murine colitis reveals a disease-associated bacteriophage community. United States. doi:10.1038/s41564-018-0210-y.
Duerkop, Breck A., Kleiner, Manuel, Paez-Espino, David, Zhu, Wenhan, Bushnell, Brian, Hassell, Brian, Winter, Sebastian E., Kyrpides, Nikos C., and Hooper, Lora V. Mon . "Murine colitis reveals a disease-associated bacteriophage community". United States. doi:10.1038/s41564-018-0210-y. https://www.osti.gov/servlets/purl/1543763.
@article{osti_1543763,
title = {Murine colitis reveals a disease-associated bacteriophage community},
author = {Duerkop, Breck A. and Kleiner, Manuel and Paez-Espino, David and Zhu, Wenhan and Bushnell, Brian and Hassell, Brian and Winter, Sebastian E. and Kyrpides, Nikos C. and Hooper, Lora V.},
abstractNote = {The dysregulation of intestinal microbial communities is associated with inflammatory bowel diseases (IBD). Studies aimed at understanding the contribution of the microbiota to inflammatory diseases have primarily focused on bacteria, yet the intestine harbours a viral component dominated by prokaryotic viruses known as bacteriophages (phages). Phage numbers are elevated at the intestinal mucosal surface and phages increase in abundance during IBD, suggesting that phages play an unidentified role in IBD. We used a sequence-independent approach for the selection of viral contigs and then applied quantitative metagenomics to study intestinal phages in a mouse model of colitis. We discovered that during colitis the intestinal phage population is altered and transitions from an ordered state to a stochastic dysbiosis. We identified phages specific to pathobiotic hosts associated with intestinal disease, whose abundances are altered during colitis. Additionally, phage populations in healthy and diseased mice overlapped with phages from healthy humans and humans with IBD. Our findings indicate that intestinal phage communities are altered during inflammatory disease, establishing a platform for investigating phage involvement in IBD.},
doi = {10.1038/s41564-018-0210-y},
journal = {Nature Microbiology},
number = [9],
volume = [3],
place = {United States},
year = {2018},
month = {7}
}

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