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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. https://doi.org/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. https://doi.org/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 = {Mon Jul 23 00:00:00 EDT 2018},
month = {Mon Jul 23 00:00:00 EDT 2018}
}

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journal, June 2019


How diet and the microbiome shape health or contribute to disease: A mini-review of current models and clinical studies
journal, January 2019

  • Zangara, Megan T.; McDonald, Christine
  • Experimental Biology and Medicine, Vol. 244, Issue 6
  • DOI: 10.1177/1535370219826070

Turning the “Phage” on Malnutrition and Stunting
journal, February 2020


Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System
journal, September 2019


Using Twitter to Understand the Human Bowel Disease Community: Exploratory Analysis of Key Topics
journal, January 2019

  • Pérez-Pérez, Martín; Pérez-Rodríguez, Gael; Fdez-Riverola, Florentino
  • Journal of Medical Internet Research, Vol. 21, Issue 8
  • DOI: 10.2196/12610

Gut Microbiota beyond Bacteria—Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD
journal, April 2020

  • Matijašić, Mario; Meštrović, Tomislav; Čipčić Paljetak, Hana
  • International Journal of Molecular Sciences, Vol. 21, Issue 8
  • DOI: 10.3390/ijms21082668

IMG/VR v.2.0: an integrated data management and analysis system for cultivated and environmental viral genomes
journal, November 2018

  • Paez-Espino, David; Roux, Simon; Chen, I-Min A.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1127

Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System
journal, September 2019


Bacteriophages shift the focus of the mammalian microbiota
journal, October 2018


Using Twitter to Understand the Human Bowel Disease Community: Exploratory Analysis of Key Topics
journal, January 2019

  • Pérez-Pérez, Martín; Pérez-Rodríguez, Gael; Fdez-Riverola, Florentino
  • Journal of Medical Internet Research, Vol. 21, Issue 8
  • DOI: 10.2196/12610

Considering the Other Half of the Gut Microbiome: Bacteriophages
journal, June 2019


Demographic and environmental drivers of metagenomic viral diversity in vampire bats
journal, October 2019

  • Bergner, Laura M.; Orton, Richard J.; Benavides, Julio A.
  • Molecular Ecology, Vol. 29, Issue 1
  • DOI: 10.1111/mec.15250

Studying the gut virome in the metagenomic era: challenges and perspectives
journal, October 2019


More than Simple Parasites: the Sociobiology of Bacteriophages and Their Bacterial Hosts
journal, April 2020