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


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.

SUBMITTER: Reber SO 

PROVIDER: S-EPMC4896712 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Reber Stefan O SO   Siebler Philip H PH   Donner Nina C NC   Morton James T JT   Smith David G DG   Kopelman Jared M JM   Lowe Kenneth R KR   Wheeler Kristen J KJ   Fox James H JH   Hassell James E JE   Greenwood Benjamin N BN   Jansch Charline C   Lechner Anja A   Schmidt Dominic D   Uschold-Schmidt Nicole N   Füchsl Andrea M AM   Langgartner Dominik D   Walker Frederick R FR   Hale Matthew W MW   Lopez Perez Gerardo G   Van Treuren Will W   González Antonio A   Halweg-Edwards Andrea L AL   Fleshner Monika M   Raison Charles L CL   Rook Graham A GA   Peddada Shyamal D SD   Knight Rob R   Lowry Christopher A CA  

Proceedings of the National Academy of Sciences of the United States of America 20160516 22


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  ...[more]

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