Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut
Open accessAbstract
Significance: A consortium of sequenced human gut bacteria was introduced into germ-free mice followed by a “staged” phage attack with virus-like particles purified from the fecal microbiota of five healthy adult humans. Unique phages were identified attacking microbiota members in nonsimultaneous fashion. Some host bacterial species acquired resistance to phage attack through ecological or epigenetic mechanisms. Changes in community structure observed after attack were transient. Spontaneous induction of prophages present in seven bacterial taxa was modest, occurring independently of the phage attack. Together, these results reveal a largely temperate phage–bacterial host dynamic and illustrate how gnotobiotic mouse models can help characterize ecological relationships in the gut by taking into account its most abundant but least understood component, viruses.
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Gnotobiotic systems allow precise control of microbial composition, enabling dissection of how specific bacteria influence phage pharmacokinetics, biodistribution, and therapeutic efficacy.
“These systems allow precise control of microbial composition, enabling the dissection of how specific bacteria influence phage pharmacokinetics, biodistribution, and therapeutic efficacy.”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [118]
The Abstract describes a defined 15-member bacterial community used to study phage–bacterial dynamics. The section “Nonsimultaneous Detection of Viruses and Community Rearrangements” reports phage persistence and distribution across gut segments, but does not establish how specific bacteria affect phage pharmacokinetics or biodistribution. The paper mentions candidate therapeutic agents; it does not test therapeutic efficacy. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGnotobiotic mice provide unparalleled mechanistic insight into phage-bacteria-host immunity interactions.
“Given the interplay between phages, bacteria, and host immunity, gnotobiotic mice provide unparalleled mechanistic insight [20,118]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [118]
The Prospectus describes gnotobiotic mice as a tractable, more realistic-than-in-vitro system for characterizing phage–bacterial dynamics. The Results and Discussion report immune measurements only to check for differences between treatment groups; they do not establish mechanistic insight into interactions with host immunity. The paper also does not support the stronger claim that the insight is 'unparalleled.' Page numbers are unavailable in our copy. (LLM, conf=0.86)
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- Authors
- Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L., & Gordon, J. I.
- Affiliations
- Washington University in St. Louis (US)
- San Diego State University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-11-20
- Volume
- 110
- Issue
- 50
- Pages
- 20236-20241
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3864308
- OpenAlex
- W2057460314
- Cited by
- 355
- References
- 4
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 25 · 2023: 31 · 2022: 28 · 2021: 36 · 2020: 42 · 2019: 44 · 2018: 26 · 2017: 22 · 2016: 21 · 2015: 22 · 2014: 19 · 2013: 2
- FWCI
- 18.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation of America
- Crohn's and Colitis Foundation
- National Institutes of Health (DK078669)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK030292, DK-30292, DK078669, P01DK078669, DK078669S1, R01DK030292)
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- bacteriophages, phage-bacteria interactions, gut microbiota, gnotobiotic mice, germ-free mice, prophages, Bacteroides cellulosilyticus, phage resistance, virus-like particles, transposon mutants, host fitness
- MeSH terms
- Animals, Bacteroides, Base Sequence, Cell Count, Feces, Flow Cytometry, Germ-Free Life, Humans, Molecular Sequence Data, Genetic Variation, Polymerase Chain Reaction, Sequence Analysis, DNA, DNA Primers, Models, Animal, Prophages, Gastrointestinal Tract, Mice, Host-Pathogen Interactions, Clustered Regularly Interspaced Short Palindromic Repeats
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