Virus-induced perturbations in the mouse microbiome are impacted by microbial experience

ABSTRACT The bacterial microbiome has a major impact on health and can shape metabolism, host tolerance, immune responses, and the outcome of future infections. The bacterial microbiome is highly variable between individuals. Specific pathogen-free animals have reduced microbiome diversity, making i...

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Main Authors: Shanley N. Roach, Wendy Phillips, Lauren M. Pross, Autumn E. Sanders, Mark J. Pierson, Ryan C. Hunter, Ryan A. Langlois
Format: Article
Language:English
Published: American Society for Microbiology 2025-03-01
Series:mSphere
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Online Access:https://journals.asm.org/doi/10.1128/msphere.00563-24
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author Shanley N. Roach
Wendy Phillips
Lauren M. Pross
Autumn E. Sanders
Mark J. Pierson
Ryan C. Hunter
Ryan A. Langlois
author_facet Shanley N. Roach
Wendy Phillips
Lauren M. Pross
Autumn E. Sanders
Mark J. Pierson
Ryan C. Hunter
Ryan A. Langlois
author_sort Shanley N. Roach
collection DOAJ
description ABSTRACT The bacterial microbiome has a major impact on health and can shape metabolism, host tolerance, immune responses, and the outcome of future infections. The bacterial microbiome is highly variable between individuals. Specific pathogen-free animals have reduced microbiome diversity, making it difficult to evaluate the impact of infection-induced microbiome disruption that would be observed in free-living animals, including people. Mice are commonly used as a preclinical model but unfortunately often fail to predict translation success or failure, particularly for immune and infectious disease-targeting therapies. Here, we utilize pet store mouse cohoused “dirty” mice with diverse microbial experience to explore how host variability and infection may be interacting to drive unique microbiome changes. We found that cohoused animals had significantly increased bacterial diversity in the small intestine and cecum but not in the large intestine. There were differentially abundant taxa between clean and dirty animals in all three tissues. After infection with influenza A virus, samples clustered by both housing condition and infection status in the cecum and large intestine, while small intestine samples clustered predominantly by infection. Altogether, these results highlight the differential impact of housing, infection, and interaction between the two in dictating community composition across the gastrointestinal microbiome.IMPORTANCETraditionally housed pathogen-free mouse models do not fully capture the natural variability observed among human microbiomes, which may underlie their poor translationally predictive value. Understanding the difference between pathogen-induced shifts in the bacterial microbiome and natural microbiome variance is a major hurdle to determining bacterial biomarkers of disease. It is also critical to understand how diverse baseline microbiomes may be differentially impacted by infection and contribute to disease. Pet store cohoused “dirty” mice have diverse microbial experiences and microbiomes, allowing us to evaluate how baseline variation, infection, and interaction between the two impact the microbiome.
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spelling doaj-art-061cc4bf5d7744e9bcf3cc4660f0dab62025-08-20T02:40:33ZengAmerican Society for MicrobiologymSphere2379-50422025-03-0110310.1128/msphere.00563-24Virus-induced perturbations in the mouse microbiome are impacted by microbial experienceShanley N. Roach0Wendy Phillips1Lauren M. Pross2Autumn E. Sanders3Mark J. Pierson4Ryan C. Hunter5Ryan A. Langlois6Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University at Buffalo, Getzville, New York, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAABSTRACT The bacterial microbiome has a major impact on health and can shape metabolism, host tolerance, immune responses, and the outcome of future infections. The bacterial microbiome is highly variable between individuals. Specific pathogen-free animals have reduced microbiome diversity, making it difficult to evaluate the impact of infection-induced microbiome disruption that would be observed in free-living animals, including people. Mice are commonly used as a preclinical model but unfortunately often fail to predict translation success or failure, particularly for immune and infectious disease-targeting therapies. Here, we utilize pet store mouse cohoused “dirty” mice with diverse microbial experience to explore how host variability and infection may be interacting to drive unique microbiome changes. We found that cohoused animals had significantly increased bacterial diversity in the small intestine and cecum but not in the large intestine. There were differentially abundant taxa between clean and dirty animals in all three tissues. After infection with influenza A virus, samples clustered by both housing condition and infection status in the cecum and large intestine, while small intestine samples clustered predominantly by infection. Altogether, these results highlight the differential impact of housing, infection, and interaction between the two in dictating community composition across the gastrointestinal microbiome.IMPORTANCETraditionally housed pathogen-free mouse models do not fully capture the natural variability observed among human microbiomes, which may underlie their poor translationally predictive value. Understanding the difference between pathogen-induced shifts in the bacterial microbiome and natural microbiome variance is a major hurdle to determining bacterial biomarkers of disease. It is also critical to understand how diverse baseline microbiomes may be differentially impacted by infection and contribute to disease. Pet store cohoused “dirty” mice have diverse microbial experiences and microbiomes, allowing us to evaluate how baseline variation, infection, and interaction between the two impact the microbiome.https://journals.asm.org/doi/10.1128/msphere.00563-24microbiomeinfluenza virusdysbiosisdirty mice
spellingShingle Shanley N. Roach
Wendy Phillips
Lauren M. Pross
Autumn E. Sanders
Mark J. Pierson
Ryan C. Hunter
Ryan A. Langlois
Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
mSphere
microbiome
influenza virus
dysbiosis
dirty mice
title Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
title_full Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
title_fullStr Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
title_full_unstemmed Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
title_short Virus-induced perturbations in the mouse microbiome are impacted by microbial experience
title_sort virus induced perturbations in the mouse microbiome are impacted by microbial experience
topic microbiome
influenza virus
dysbiosis
dirty mice
url https://journals.asm.org/doi/10.1128/msphere.00563-24
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AT autumnesanders virusinducedperturbationsinthemousemicrobiomeareimpactedbymicrobialexperience
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