Summary: According to a new study, mice injected with a specific bacterium became more resilient to stress, showing less anxiety and fear in stressful situations.
Source: UCL.
Injecting mice with a UCL-discovered bacterium can reduce stress and inflammation, preventing them from developing PTSD-like conditions, finds a new international study led by the University of Colorado Boulder.
The research, published in Proceedings of the National Academy of Sciences, found that mice injected with the bacterium were more resilient to stress, showing less fear and anxiety in stressful situations. The immunization also changed serotonin activity in the brain, with similar beneficial effects to antidepressants or long-term exercise. Additionally, immunized mice were protected against colon inflammation which was caused or worsened by stress in unimmunized mice.
The bacterium, Mycobacterium vaccae (M. vaccae), is found naturally in soil and was first isolated and characterised at UCL by Professor John Stanford. Its immunological properties were investigated by Professor Graham Rook (UCL Infection & Immunity), a co-author on the new study. “The idea that a bacterium found in soil could prevent serious mental health problems might sound far-fetched, but bacteria can have a profound effect on both mental and physical health,” says Professor Rook. “Microorganisms in our bodies play a vital role regulating our immune systems and can help to reduce inflammation. As well as causing physical problems, inflammation is also a risk factor for several psychiatric disorders. Previous research has found that US Marines with evidence of inflammation in their body are more likely to develop PTSD, and the latest work suggests that bacterial immunization might help to reduce this risk. It shows that M. vaccae simultaneously prevents colitis and psychiatric symptoms by switching on regulatory pathways in the immune system.”
The study supports the ‘old friends’ hypothesis, which was first proposed by Professor Rook in 2003 as an update of the ‘hygiene hypothesis’.
“Our ancestors lived among a rich variety of microorganisms and our immune system evolved to function in this environment,” explains Professor Rook. “We now have much less contact with common microorganisms such as soil bacteria and our diets have changed leaving fewer nutrients available to gut bacteria. Without these ‘old friends’ helping to regulate the immune system, we are left at higher risk of inflammatory diseases and psychiatric disorders linked to chronic low-level inflammation. The new study supports the strategy of re-introducing humans to their ‘old friends’ to improve both mental and physical health.”
To test the effect of the M. vaccae bacteria on stress resilience, the researchers injected male mice with either a heat-killed sample of the bacterium or a placebo. The mice were then housed individually or with a dominant male for 19 days. Living with a dominant male is stressful and leads to submissive behaviour.
Mice that had been given M. vaccae were better at coping in this situation, acting less submissively and spending less time fleeing from or avoiding the dominant male. They were also less fearful and more willing to explore open environments when they were taken out of the housing on day 20. Previous studies in rodents and humans suggest that this response is a marker for reduced vulnerability to long-term anxiety and depressive-like symptoms.
“The immunized mice responded with a more proactive behavioural coping response to stress, a strategy that has been associated with stress resilience in animals and humans,” says Professor Christopher Lowry from the University of Colorado Boulder, senior author of the new research. “An injection of M. vaccae is not designed to target a particular antigen the way a vaccine would, but instead activates the individual’s immunoregulatory responses to protect from inappropriate inflammation.”
Funding: This study was supported in part by a 2010 NARSAD Young Investigator Award (to C.A.L.); German Research Foundation Grant RE 2911/5-1 (to S.O.R.); the University of Colorado Boulder (C.A.L.); Award NSF-IOS 0845550 (to C.A.L.); and donations through the CU Foundation. The research of S.D.P. was supported, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES101744-04).
Source: Harry Dayantis – UCL
Image Source: This NeuroscienceNews.com image is adapted from the UCL press release.
Original Research: Full open access research for “Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice” by 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 Jr., Benjamin N. Greenwood, Charline Jansch, Anja Lechner, Dominic Schmidt, Nicole Uschold-Schmidt, Andrea M. Füchsl, Dominik Langgartner, Frederick R. Walker, Matthew W. Hale, Gerardo Lopez Perez, Will Van Treuren, Antonio González, Andrea L. Halweg-Edwards, Monika Fleshner, Charles L. Raison, Graham A. Rook, Shyamal D. Peddada, Rob Knight, and Christopher A. Lowry in PNAS. Published online May 16 2016 doi:10.1073/pnas.1600324113
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Abstract
Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice
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. vaccaeprevented 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.
“Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccaepromotes stress resilience in mice” by 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 Jr., Benjamin N. Greenwood, Charline Jansch, Anja Lechner, Dominic Schmidt, Nicole Uschold-Schmidt, Andrea M. Füchsl, Dominik Langgartner, Frederick R. Walker, Matthew W. Hale, Gerardo Lopez Perez, Will Van Treuren, Antonio González, Andrea L. Halweg-Edwards, Monika Fleshner, Charles L. Raison, Graham A. Rook, Shyamal D. Peddada, Rob Knight, and Christopher A. Lowry in PNAS. Published online May 16 2016 doi:10.1073/pnas.1600324113