Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice
OPEN Proceedings of the National Academy of Sciences of the United States of America | 18 May 2016
SO Reber, PH Siebler, NC Donner, JT Morton, DG Smith, JM Kopelman, KR Lowe, KJ Wheeler, JH Fox, JE Hassell, BN Greenwood, C Jansch, A Lechner, D Schmidt, N Uschold-Schmidt, AM Füchsl, D Langgartner, FR Walker, MW Hale, G Lopez Perez, W Van Treuren, A González, AL Halweg-Edwards, M Fleshner, CL Raison, GA Rook, SD Peddada, R Knight and CA Lowry
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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