Reber, SO; Siebler, PH; Donner, NC; Morton, JT; Smith, DG; Kopelman, JM; Lowe, KR; ... Lowry, CA; + view all Reber, SO; Siebler, PH; Donner, NC; Morton, JT; Smith, DG; Kopelman, JM; Lowe, KR; Wheeler, KJ; Fox, JH; Hassell, JE; Greenwood, BN; Jansch, C; Lechner, A; Schmidt, D; Uschold-Schmidt, N; Füchsl, AM; Langgartner, D; Walker, FR; Hale, MW; Lopez Perez, G; Van Treuren, W; González, A; Halweg-Edwards, AL; Fleshner, M; Raison, CL; Rook, GA; Peddada, SD; Knight, R; Lowry, CA; - view fewer (2016) Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proceedings of the National Academy of Sciences of the United States of America , 113 (22) E3130-E3139. 10.1073/pnas.1600324113.

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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.

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