Evidence map›Paper›PMID 27185913›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

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

Stefan O Reber, Philip H Siebler, Nina C Donner, James T Morton, David G Smith, Jared M Kopelman, Kenneth R Lowe, Kristen J Wheeler, James H Fox, James E Hassell and 19 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
15.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 228 citations in OpenAlex.

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44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 4 countries.

Stefan O ReberLaboratory 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;
Philip H SieblerDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Nina C DonnerDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
James T MortonDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
David G SmithDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Jared M KopelmanDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Kenneth R LoweDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Kristen J WheelerDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
James H FoxDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
James E HassellDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Benjamin N GreenwoodDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Charline JanschDepartment of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
Anja LechnerInstitute of Immunology, University of Regensburg, D-93042 Regensburg, Germany;
Dominic SchmidtInstitute of Immunology, University of Regensburg, D-93042 Regensburg, Germany;
Nicole Uschold-SchmidtDepartment of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
Andrea M FüchslDepartment of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
Dominik LanggartnerDepartment of Behavioral and Molecular Neurobiology, University of Regensburg, D-93053 Regensburg, Germany;
Frederick R WalkerSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan 2308, Australia;
Matthew W HaleSchool of Psychological Science, La Trobe University, Bundoora 3086, Australia;
Gerardo Lopez PerezDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Will Van TreurenBiofrontiers Institute, University of Colorado Boulder, Boulder, CO 80309;
Antonio GonzálezDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093; Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093;
Andrea L Halweg-EdwardsDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309;
Monika FleshnerDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309;
Charles L RaisonDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093; School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706;
Graham A RookCenter for Clinical Microbiology, UCL (University College London), London WC1E 6BT, United Kingdom;
Shyamal D PeddadaBiostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709;
Rob KnightDepartment 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.
Christopher A LowryDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309; christopher.lowry@colorado.edu.ORCID 0000-0003-3920-5575
University of Colorado Boulder · USUniversity of Regensburg · DEUniversity of California San Diego · USLa Trobe University · AUNational Institute of Environmental Health Sciences · USUniversität Ulm · DEUniversity College London · GBUniversity of Newcastle Australia · AUUniversity of Wisconsin–Madison · US

Funding

Statistical Theory and Methodology with Applications toZ01ES101744 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDDADA, SHYAMAL · 2004 to 2008
$803k
Collaborative research in environmental health sciencesZIAES103066 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDDADA, SHYAMAL · 2012 to 2017
$732k
Intramural NIH HHS Z01 ES101744
6 · The paper itself

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.

Indexed as

Behavior, AnimalAnimalsAnxietyBacterial VaccinesColitisImmunizationMaleMiceMice, Inbred C57BLMycobacteriumStress, PsychologicalT-Lymphocytes, RegulatoryVaccines, InactivatedBacterial VaccinesVaccines, Inactivatedanxietychronic psychosocial stressfearmicrobiotaposttraumatic stress disorder

Identifiers

PMID27185913
PMCPMC4896712
OpenAlexW2403674481

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.