Cited by 233Stress Responses and CortisolTryptophan and brain disordersVagus Nerve Stimulation Research

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

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Reber, Stefan O., Siebler, Philip H., Donner, Nina C., Morton, James T., Smith, David G., Kopelman, Jared M., Lowe, Kenneth R., Wheeler, Kristen J. +21 more·2016·Proceedings of the National Academy of Sciences

Abstract

Significance: The hygiene, or “old friends,” hypothesis proposes that lack of exposure to immunoregulatory microorganisms in modern urban societies is resulting in an epidemic of inflammatory disease, as well as psychiatric disorders in which chronic, low-level inflammation is a risk factor. An important determinant of immunoregulation is the microbial community occupying the host organism, collectively referred to as the microbiota. Here we show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Treatment of mice with a heat-killed preparation of an immunoregulatory environmental microorganism, Mycobacterium vaccae , prevents stress-induced pathology. These data support a strategy of “reintroducing” humans to their old friends to promote optimal health and wellness.

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  • In a murine model of PTSD, immunization with a heat-killed preparation of Mycobacterium vaccae induced a more proactive behavioral response to a psychosocial stressor.

    “A study using a murine model of PTSD (170) has demonstrated that immunization with a heat-killed preparation of the immunoregulatory bacterium Mycobacterium vaccae (NCTC 11659) induced a more proactive behavioral response to a psychosocial stressor (171).”

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  1. Savignac HM, Kiely B, Dinan TG, Cryan JF (2014) Bifidobacteria exert strain-specific ef- fects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 26(11):1615-1627.

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Authors
Reber, S. O., Siebler, P. H., Donner, N. C., Morton, J. T., Smith, D. G., Kopelman, J. M., Lowe, K. R., Wheeler, K. J., Fox, J. H., Hassell, J. E., Greenwood, B. N., Jansch, C., Lechner, A., Schmidt, D., Uschold-Schmidt, N., Füchsl, A. M., Langgartner, D., Walker, F. R., Hale, M. W., Lopez Perez, G., Van Treuren, W., González, A., Halweg-Edwards, A. L., Fleshner, M., Raison, C. L., Rook, G. A., Peddada, S. D., Knight, R., & Lowry, C. A.
Affiliations
  • Universität Ulm (DE)
  • University of Colorado Boulder (US)
  • University of Regensburg (DE)
  • Department of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
  • University of Newcastle Australia (AU)
  • La Trobe University (AU)
  • Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309;
  • Biofrontiers Institute, University of Colorado Boulder, Boulder, CO 80309;
  • University of California San Diego (US)
  • Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309;
  • University of Wisconsin–Madison (US)
  • University College London (GB)
  • National Institutes of Health (US)
Venue
Proceedings of the National Academy of Sciences
Published
2016-05-16
Volume
113
Issue
22
Pages
E3130-9
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2403674481
Cited by
233
References
136
Citations by year
2026: 13 · 2025: 16 · 2024: 30 · 2023: 18 · 2022: 28 · 2021: 21 · 2020: 18 · 2019: 25 · 2018: 31 · 2017: 19 · 2016: 14
FWCI
18.95
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • Figshare (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion, other-oa)
Funders
  • NSF (NSF-IOS #0845550)
  • German Research Foundation (RE 2911/5-1)
  • HHS | NIH | National Institute of Environmental Health Sciences (Z01 ES101744-04)
  • CU Foundation (N.A.)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
Mycobacterium vaccae, psychosocial stress, inflammatory bowel disease, gut microbiota, regulatory T cells, anxiety-like behavior, fear behavior, microbiota-based therapy, stress resilience
MeSH terms
Animals, Anxiety, Bacterial Vaccines, Behavior, Animal, Colitis, Immunization, Male, Mice, Inbred C57BL, Mycobacterium, Stress, Psychological, Vaccines, Inactivated, T-Lymphocytes, Regulatory, Mice

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