Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3130-9. doi: 10.1073/pnas.1600324113. Epub 2016 May 16.

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

Author information

1
Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, University of Ulm, D-89081 Ulm, Germany; Department of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
2
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
3
Department of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
4
Institute of Immunology, University of Regensburg, D-93042 Regensburg, Germany;
5
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan 2308, Australia;
6
School of Psychological Science, La Trobe University, Bundoora 3086, Australia;
7
Biofrontiers Institute, University of Colorado Boulder, Boulder, CO 80309;
8
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093;
9
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309;
10
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706;
11
Center for Clinical Microbiology, UCL (University College London), London WC1E 6BT, United Kingdom;
12
Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709;
13
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093; Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093.
14
Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309; christopher.lowry@colorado.edu.

Abstract

The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies.

KEYWORDS:

anxiety; chronic psychosocial stress; fear; microbiota; posttraumatic stress disorder

PMID:
27185913
PMCID:
PMC4896712
DOI:
10.1073/pnas.1600324113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center