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:
-
[1];
[2];
[3];
[4];
[4]
- Univ. of Colorado School of Medicine, Aurora, CO (United States)
- North Carolina State Univ., Raleigh, NC (United States)
- USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
- Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (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 = {2018},
month = {7}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 32 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Assessment of viral community functional potential from viral metagenomes may be hampered by contamination with cellular sequences
journal, December 2013
- Roux, Simon; Krupovic, Mart; Debroas, Didier
- Open Biology, Vol. 3, Issue 12
Inflammatory Bowel Disease
journal, November 2009
- Abraham, Clara; Cho, Judy H.
- New England Journal of Medicine, Vol. 361, Issue 21
Benchmarking viromics: an in silico evaluation of metagenome-enabled estimates of viral community composition and diversity
journal, January 2017
- Roux, Simon; Emerson, Joanne B.; Eloe-Fadrosh, Emiley A.
- PeerJ, Vol. 5
A new perspective on lysogeny: prophages as active regulatory switches of bacteria
journal, September 2015
- Feiner, Ron; Argov, Tal; Rabinovich, Lev
- Nature Reviews Microbiology, Vol. 13, Issue 10
T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade
journal, February 2009
- Ostanin, Dmitry V.; Bao, Jianxiong; Koboziev, Iurii
- American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 296, Issue 2
The Binning of Metagenomic Contigs for Microbial Physiology of Mixed Cultures
journal, January 2012
- Strous, Marc; Kraft, Beate; Bisdorf, Regina
- Frontiers in Microbiology, Vol. 3
The human gut virome: Inter-individual variation and dynamic response to diet
journal, August 2011
- Minot, S.; Sinha, R.; Chen, J.
- Genome Research, Vol. 21, Issue 10
Inflammation boosts bacteriophage transfer between Salmonella spp.
journal, March 2017
- Diard, Médéric; Bakkeren, Erik; Cornuault, Jeffrey K.
- Science, Vol. 355, Issue 6330
Causes for the intriguing presence of tRNAs in phages
journal, September 2007
- Bailly-Bechet, M.; Vergassola, M.; Rocha, E.
- Genome Research, Vol. 17, Issue 10
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences
journal, May 2006
- Li, W.; Godzik, A.
- Bioinformatics, Vol. 22, Issue 13
ARAGORN, a program to detect tRNA genes and tmRNA genes in nucleotide sequences
journal, January 2004
- Laslett, Dean; Canback, Bjorn
- Nucleic Acids Research, Vol. 32, Issue 1, p. 11-16
Pretreatment of Mice with Streptomycin Provides a Salmonella enterica Serovar Typhimurium Colitis Model That Allows Analysis of Both Pathogen and Host
journal, May 2003
- Barthel, M.; Hapfelmeier, S.; Quintanilla-Martinez, L.
- Infection and Immunity, Vol. 71, Issue 5
The Complete Nucleotide Sequence of Bacteriophage HP1 DNA
journal, June 1996
- Esposito, D.; Fitzmaurice, W. P.; Benjamin, R. C.
- Nucleic Acids Research, Vol. 24, Issue 12
Viruses in the faecal microbiota of monozygotic twins and their mothers
journal, July 2010
- Reyes, Alejandro; Haynes, Matthew; Hanson, Nicole
- Nature, Vol. 466, Issue 7304
Dysbiosis in inflammatory bowel disease: a role for bacteriophages?
journal, March 2008
- Lepage, P.; Colombet, J.; Marteau, P.
- Gut, Vol. 57, Issue 3
Nontargeted virus sequence discovery pipeline and virus clustering for metagenomic data
journal, July 2017
- Paez-Espino, David; Pavlopoulos, Georgios A.; Ivanova, Natalia N.
- Nature Protocols, Vol. 12, Issue 8
Host-Mediated Inflammation Disrupts the Intestinal Microbiota and Promotes the Overgrowth of Enterobacteriaceae
journal, September 2007
- Lupp, Claudia; Robertson, Marilyn L.; Wickham, Mark E.
- Cell Host & Microbe, Vol. 2, Issue 3
Molecular Basis for Lytic Bacteriophage Resistance in Enterococci
journal, August 2016
- Duerkop, Breck A.; Huo, Wenwen; Bhardwaj, Pooja
- mBio, Vol. 7, Issue 4
Diverse CRISPRs Evolving in Human Microbiomes
journal, June 2012
- Rho, Mina; Wu, Yu-Wei; Tang, Haixu
- PLoS Genetics, Vol. 8, Issue 6, Article No. e1002441
An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
journal, July 2005
- Mazmanian, Sarkis K.; Liu, Cui Hua; Tzianabos, Arthur O.
- Cell, Vol. 122, Issue 1
H OW H OST -M ICROBIAL I NTERACTIONS S HAPE THE N UTRIENT E NVIRONMENT OF THE M AMMALIAN I NTESTINE
journal, July 2002
- Hooper, Lora V.; Midtvedt, Tore; Gordon, Jeffrey I.
- Annual Review of Nutrition, Vol. 22, Issue 1
In silico analysis of AHJD-like viruses, Staphylococcus aureus phages S24-1 and S13′, and study of phage S24-1 adsorption
journal, March 2014
- Uchiyama, Jumpei; Takemura-Uchiyama, Iyo; Kato, Shin-ichiro
- MicrobiologyOpen, Vol. 3, Issue 2
Computational approaches to predict bacteriophage–host relationships
journal, December 2015
- Edwards, Robert A.; McNair, Katelyn; Faust, Karoline
- FEMS Microbiology Reviews, Vol. 40, Issue 2
VirSorter: mining viral signal from microbial genomic data
journal, January 2015
- Roux, Simon; Enault, Francois; Hurwitz, Bonnie L.
- PeerJ, Vol. 3
Divergent extremes but convergent recovery of bacterial and archaeal soil communities to an ongoing subterranean coal mine fire
journal, March 2017
- Lee, Sang-Hoon; Sorensen, Jackson W.; Grady, Keara L.
- The ISME Journal, Vol. 11, Issue 6
RAG-1-deficient mice have no mature B and T lymphocytes
journal, March 1992
- Mombaerts, Peter; Iacomini, John; Johnson, Randall S.
- Cell, Vol. 68, Issue 5
The microbiota in inflammatory bowel disease
journal, March 2015
- Sheehan, Donal; Moran, Carthage; Shanahan, Fergus
- Journal of Gastroenterology, Vol. 50, Issue 5
Large Variabilities in Host Strain Susceptibility and Phage Host Range Govern Interactions between Lytic Marine Phages and Their Flavobacterium Hosts
journal, August 2007
- Holmfeldt, K.; Middelboe, M.; Nybroe, O.
- Applied and Environmental Microbiology, Vol. 73, Issue 21
Bacteriophage adhering to mucus provide a non-host-derived immunity
journal, May 2013
- Barr, J. J.; Auro, R.; Furlan, M.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 26
IMG/VR: a database of cultured and uncultured DNA Viruses and retroviruses
journal, October 2016
- Paez-Espino, David; Chen, I. -Min A.; Palaniappan, Krishna
- Nucleic Acids Research, Vol. 45, Issue D1
Uncovering Earth’s virome
journal, August 2016
- Paez-Espino, David; Eloe-Fadrosh, Emiley A.; Pavlopoulos, Georgios A.
- Nature, Vol. 536, Issue 7617
Functional metagenomic profiling of nine biomes
journal, March 2008
- Dinsdale, Elizabeth A.; Edwards, Robert A.; Hall, Dana
- Nature, Vol. 452, Issue 7187
The dynamics of gut-associated microbial communities during inflammation
journal, March 2013
- Winter, Sebastian E.; Lopez, Christopher A.; Bäumler, Andreas J.
- EMBO reports, Vol. 14, Issue 4
IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth
journal, April 2012
- Peng, Y.; Leung, H. C. M.; Yiu, S. M.
- Bioinformatics, Vol. 28, Issue 11
The SILVA ribosomal RNA gene database project: improved data processing and web-based tools
journal, November 2012
- Quast, Christian; Pruesse, Elmar; Yilmaz, Pelin
- Nucleic Acids Research, Vol. 41, Issue D1
Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis
journal, May 2012
- Berry, David; Schwab, Clarissa; Milinovich, Gabriel
- The ISME Journal, Vol. 6, Issue 11
Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease
journal, January 2015
- Norman, Jason M.; Handley, Scott A.; Baldridge, Megan T.
- Cell, Vol. 160, Issue 3
Suppression of Clostridium difficile in the Gastrointestinal Tracts of Germfree Mice Inoculated with a Murine Isolate from the Family Lachnospiraceae
journal, August 2012
- Reeves, Angela E.; Koenigsknecht, Mark J.; Bergin, Ingrid L.
- Infection and Immunity, Vol. 80, Issue 11
Orthologous Gene Clusters and Taxon Signature Genes for Viruses of Prokaryotes
journal, December 2012
- Kristensen, D. M.; Waller, A. S.; Yamada, T.
- Journal of Bacteriology, Vol. 195, Issue 5
Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin
journal, August 2006
- Cash, H. L.
- Science, Vol. 313, Issue 5790
Role of the Microbiota in Immunity and Inflammation
journal, March 2014
- Belkaid, Yasmine; Hand, Timothy W.
- Cell, Vol. 157, Issue 1
Healthy human gut phageome
journal, August 2016
- Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 37
BLAST+: architecture and applications
journal, January 2009
- Camacho, Christiam; Coulouris, George; Avagyan, Vahram
- BMC Bioinformatics, Vol. 10, Issue 1
Temporal Stability of the Human Skin Microbiome
journal, May 2016
- Oh, Julia; Byrd, Allyson L.; Park, Morgan
- Cell, Vol. 165, Issue 4
Changes in assembly processes in soil bacterial communities following a wildfire disturbance
journal, February 2013
- Ferrenberg, Scott; O'Neill, Sean P.; Knelman, Joseph E.
- The ISME Journal, Vol. 7, Issue 6
Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell- mediated immunity
journal, February 1994
- Powrie, F.
- Journal of Experimental Medicine, Vol. 179, Issue 2
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study
journal, January 2017
- Kang, Dae-Wook; Adams, James B.; Gregory, Ann C.
- Microbiome, Vol. 5, Issue 1
The genome of bacteriophage φKZ of Pseudomonas aeruginosa
journal, March 2002
- Mesyanzhinov, Vadim V.; Robben, Johan; Grymonprez, Barbara
- Journal of Molecular Biology, Vol. 317, Issue 1
An obesity-associated gut microbiome with increased capacity for energy harvest
journal, December 2006
- Turnbaugh, Peter J.; Ley, Ruth E.; Mahowald, Michael A.
- Nature, Vol. 444, Issue 7122
A composite bacteriophage alters colonization by an intestinal commensal bacterium
journal, October 2012
- Duerkop, B. A.; Clements, C. V.; Rollins, D.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 43
Genomic Organization and Molecular Characterization of Clostridium difficile Bacteriophage CD119
journal, March 2006
- Govind, R.; Fralick, J. A.; Rolfe, R. D.
- Journal of Bacteriology, Vol. 188, Issue 7
Prophage Induction and Expression of Prophage-Encoded Virulence Factors in Group A Streptococcus Serotype M3 Strain MGAS315
journal, November 2003
- Banks, D. J.; Lei, B.; Musser, J. M.
- Infection and Immunity, Vol. 71, Issue 12
HMMER web server: interactive sequence similarity searching
journal, May 2011
- Finn, R. D.; Clements, J.; Eddy, S. R.
- Nucleic Acids Research, Vol. 39, Issue suppl
Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses
journal, June 2016
- Enault, François; Briet, Arnaud; Bouteille, Léa
- The ISME Journal, Vol. 11, Issue 1
Identification of a genetic determinant responsible for host specificity in Streptococcus thermophilus bacteriophages: Streptococcus thermophilus phage anti-receptor
journal, July 2001
- Duplessis, Martin; Moineau, Sylvain
- Molecular Microbiology, Vol. 41, Issue 2
Host-Derived Nitrate Boosts Growth of E. coli in the Inflamed Gut
journal, February 2013
- Winter, S. E.; Winter, M. G.; Xavier, M. N.
- Science, Vol. 339, Issue 6120
Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases With Time, Based on Systematic Review
journal, January 2012
- Molodecky, Natalie A.; Soon, Ing Shian; Rabi, Doreen M.
- Gastroenterology, Vol. 142, Issue 1
Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small Intestine
journal, October 2008
- Ivanov, Ivaylo I.; Frutos, Rosa de Llanos; Manel, Nicolas
- Cell Host & Microbe, Vol. 4, Issue 4
IMG/M: integrated genome and metagenome comparative data analysis system
journal, October 2016
- Chen, I-Min A.; Markowitz, Victor M.; Chu, Ken
- Nucleic Acids Research, Vol. 45, Issue D1
Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease
journal, February 2015
- Jiang, Weiwei; Wu, Na; Wang, Xuemei
- Scientific Reports, Vol. 5, Issue 1
Microbial Respiration and Formate Oxidation as Metabolic Signatures of Inflammation-Associated Dysbiosis
journal, February 2017
- Hughes, Elizabeth R.; Winter, Maria G.; Duerkop, Breck A.
- Cell Host & Microbe, Vol. 21, Issue 2
Evaluation of methods to purify virus-like particles for metagenomic sequencing of intestinal viromes
journal, January 2015
- Kleiner, Manuel; Hooper, Lora V.; Duerkop, Breck A.
- BMC Genomics, Vol. 16, Issue 1
Viruses of the Archaea: a unifying view
journal, November 2006
- Prangishvili, David; Forterre, Patrick; Garrett, Roger A.
- Nature Reviews Microbiology, Vol. 4, Issue 11
Inflammatory Bowel Disease
journal, March 2010
- Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S.
- Annual Review of Immunology, Vol. 28, Issue 1
Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander
journal, April 2020
- Song, Xiaoming; Nie, Fulei; Chen, Wei
- Horticulture Research, Vol. 7, Issue 1
Analysis of immune, microbiota and metabolome maturation in infants in a clinical trial of Lactobacillus paracasei CBA L74-fermented formula
journal, June 2020
- Roggero, Paola; Liotto, Nadia; Pozzi, Chiara
- Nature Communications, Vol. 11, Issue 1
Host-Mediated Inflammation Disrupts the Intestinal Microbiota and Promotes the Overgrowth of Enterobacteriaceae
journal, August 2007
- Lupp, Claudia; Robertson, Marilyn L.; Wickham, Mark E.
- Cell Host & Microbe, Vol. 2, Issue 2
Works referencing / citing this record:
Multidisciplinarity in Microbiome Research: A Challenge and Opportunity to Rethink Causation, Variability, and Scale
journal, May 2019
- Amato, Katherine R.; Maurice, Corinne F.; Guillemin, Karen
- BioEssays, Vol. 41, Issue 10
Defining the human gut host–phage network through single-cell viral tagging
journal, August 2019
- Džunková, Mária; Low, Soo Jen; Daly, Joshua N.
- Nature Microbiology, Vol. 4, Issue 12
The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new insights into complex disease
journal, September 2018
- Harris, Katharine G.; Chang, Eugene B.
- Clinical Science, Vol. 132, Issue 18
Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion
journal, December 2019
- Broggi, Achille; Granucci, Francesca; Zanoni, Ivan
- Journal of Experimental Medicine, Vol. 217, Issue 1
A critical assessment of the feature selection methods used for biomarker discovery in current metaproteomics studies
journal, June 2019
- Tang, Jing; Wang, Yunxia; Fu, Jianbo
- Briefings in Bioinformatics, Vol. 21, Issue 4
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
Cross-Domain and Viral Interactions in the Microbiome
journal, January 2019
- Rowan-Nash, Aislinn D.; Korry, Benjamin J.; Mylonakis, Eleftherios
- Microbiology and Molecular Biology Reviews, Vol. 83, Issue 1
Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System
journal, September 2019
- Sinha, Anshul; Maurice, Corinne F.
- Mediators of Inflammation, Vol. 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
Studying the gut virome in the metagenomic era: challenges and perspectives
journal, October 2019
- Garmaeva, Sanzhima; Sinha, Trishla; Kurilshikov, Alexander
- BMC Biology, Vol. 17, Issue 1
Bacteriophages shift the focus of the mammalian microbiota
journal, October 2018
- Duerkop, Breck A.
- PLOS Pathogens, Vol. 14, Issue 10
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
Microbial-Based Therapies in the Treatment of Inflammatory Bowel Disease – An Overview of Human Studies
journal, January 2019
- Basso, Paulo José; Câmara, Niels Olsen Saraiva; Sales-Campos, Helioswilton
- Frontiers in Pharmacology, Vol. 9
Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut
journal, July 2019
- Santiago-Rodriguez, Tasha M.; Hollister, Emily B.
- Viruses, Vol. 11, Issue 7