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Cited by 201Gut microbiota and healthAnimal Nutrition and PhysiologyEscherichia coli research studies

Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection

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Velazquez, Eric M., Nguyen, Henry, Heasley, Keaton T., Saechao, Cheng H., Gil, Lindsey M., Rogers, Andrew W. L., Miller, Brittany M., Rolston, Matthew R. +9 more·2019·Nature Microbiology
DOI 10.1038/s41564-019-0407-8PMC PMC6533147
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Abstract

Lack of reproducibility is a prominent problem in biomedical research. An important source of variation in animal experiments is the microbiome, but little is known about specific changes in the microbiota composition that cause phenotypic differences. Here, we show that genetically similar laboratory mice obtained from four different commercial vendors exhibited marked phenotypic variation in their susceptibility to Salmonella infection. Faecal microbiota transplant into germ-free mice replicated donor susceptibility, revealing that variability was due to changes in the gut microbiota composition. Co-housing of mice only partially transferred protection against Salmonella infection, suggesting that minority species within the gut microbiota might confer this trait. Consistent with this idea, we identified endogenous Enterobacteriaceae, a low-abundance taxon, as a keystone species responsible for variation in the susceptibility to Salmonella infection. Protection conferred by endogenous Enterobacteriaceae could be modelled by inoculating mice with probiotic Escherichia coli, which conferred resistance by using its aerobic metabolism to compete with Salmonella for resources. We conclude that a mechanistic understanding of phenotypic variation can accelerate development of strategies for enhancing the reproducibility of animal experiments.

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  • The animals' provenance, health or immune status, and history of previous testing or procedures can influence their physiology and behaviour, as well as their response to treatments, and thus impact on study outcomes.

    “The animals’ provenance, their health or immune status, and their history of previous testing or procedures can influence their physiology and behaviour, as well as their response to treatments, and thus impact on study outcomes.”

    From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [114]

    The Results show that mice from different vendors had different susceptibility to Salmonella infection, and the Abstract links that variation to their gut microbiota and to reproducibility of animal experiments. The cited paper does not establish the claim about prior testing or procedures, behaviour, or responses to treatments generally. The copy provides section labels but no page numbers. (LLM, conf=0.88)

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  • The immune or microbiological status of the animals can influence welfare, experimental variability, and scientific outcomes.

    “The immune or microbiological status of the animals can also influence welfare, experimental variability, and scientific outcomes [112–114].”

    From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [114]

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Authors
Velazquez, E. M., Nguyen, H., Heasley, K. T., Saechao, C. H., Gil, L. M., Rogers, A. W. L., Miller, B. M., Rolston, M. R., Lopez, C. A., Litvak, Y., Liou, M. J., Faber, F., Bronner, D. N., Tiffany, C. R., Byndloss, M. X., Byndloss, A. J., & Bäumler, A. J.
Affiliations
  • University of California, Davis (US)
  • University of Würzburg (DE)
Corresponding author
Bäumler, Andreas J.
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2019-03-25
Volume
4
Issue
6
Pages
1057-1064
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-019-0407-8
PMC
PMC6533147
OpenAlex
W2925100173
Cited by
201
References
5
Citations by year
2026: 19 · 2025: 32 · 2024: 27 · 2023: 20 · 2022: 23 · 2021: 38 · 2020: 28 · 2019: 13
FWCI
8.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (T32OD010931, AI112949, AI044170, T35OD010956)
  • National Institute of General Medical Sciences (R25GM056765)
  • National Institute of Allergy and Infectious Diseases (R01AI044170, R56AI112949, R37AI044170, T32AI060555, R01AI112949, R01AI096528, R01AI112445)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK058404)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
salmonellosis, host susceptibility, gut microbiota, fecal microbiota transplantation, germ-free mice, cohousing, keystone species, probiotic Escherichia coli, aerobic metabolism, interspecific competition, low-abundance taxa
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Disease Models, Animal, Enterobacteriaceae, Escherichia coli, Germ-Free Life, Mice, Inbred C57BL, Phenotype, Salmonella, Salmonella Infections, Animal, Reproducibility of Results, Biomarkers, Probiotics, Animal Experimentation, Mice, Biosynthetic Pathways, Microbial Interactions

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