Researchers have discovered that a common soil bacterium called Mycobacterium vaccae (M. vaccae) may help reduce stress, anxiety, and inflammation in the brain.
Key Facts:
- M. vaccae is a naturally occurring bacterium found in soil, mud, and water. It is considered harmless to humans.
- When heat-killed M. vaccae is injected into rats, it reduces stress-induced anxiety behaviors.
- The killed bacterium appears to induce an anti-inflammatory state in the hippocampus region of the brain.
- This anti-inflammatory effect may shield the brain against excessive inflammation caused by stress.
Source: Brain Behav Immun.
How a Soil Bacterium Could Help Shield The Brain From Stress
Stress, anxiety and inflammation are closely linked in the brain.
Stress exposure leads to anxiety behaviors in animals and humans. It also leads to excessive inflammation in the hippocampus region of the brain that is involved in emotions and memory.
Scientists have theorized that this inflammation in the hippocampus likely contributes to stress-induced anxiety.
Researchers have now discovered that inoculating rats with a heat-killed preparation of the common soil bacterium Mycobacterium vaccae (M. vaccae) reduces stress-induced anxiety behaviors.
The killed M. vaccae appears to exert these anxiety-reducing effects by inducing an anti-inflammatory state in the hippocampus. This shields the brain against excessive inflammatory responses to stressors.
M. vaccae – An “Old Friend” With Benefits
M. vaccae is an example of an “Old Friend” – a microbe that humans coevolved with over millennia.
Regular exposure to Old Friends like M. vaccae trains our immune system to regulate inflammation.
Their absence in modern urban environments may be contributing to chronic inflammatory disorders.
When injected into rats, this harmless soil bacterium appears to be sensed by the immune system as a positive signal. In response, the immune system releases more anti-inflammatory cytokines like interleukin-4 (IL-4).
These promote an “alternatively activated” state that reduces excessive inflammation.
M. vaccae Induces Anti-Inflammatory Changes in The Hippocampus
The researchers immunized adult male rats 3 times with heat-killed M. vaccae or a saline solution.
A week after the last injection, they examined the hippocampus region of the brain.
They found increased gene expression of the anti-inflammatory cytokine IL-4 and higher levels of IL-4 protein in M. vaccae immunized rats compared to controls.
Two genes considered markers of alternative macrophage activation – Cd200r1 and Mrc1 – were also elevated in the M. vaccae group.
To confirm IL-4 was causing these effects, the researchers injected recombinant IL-4 directly into the brains of rats. This mimicked the effects of M. vaccae on Cd200r1 and Mrc1.
M. vaccae May Reduce Microglial Sensitization to Stress
Microglia are immune cells in the brain that can mount inflammatory responses to threats.
Research shows that stress exposure can sensitize microglia, priming them to overreact to subsequent stressors.
The researchers found that M. vaccae reduced expression of genes implicated in microglial sensitization (Nlrp3, Nfkbia) and stress-induced inflammation.
They also discovered that M. vaccae prevented stress-induced declines in Cd200r1 – a receptor that keeps microglia in a quiescent state.
Stress reduced Cd200r1 in the hippocampus, but this effect was blocked in M. vaccae treated animals.
Disrupting Cd200r1 is known to agitate microglia.
M. vaccae Shields The Brain Against A Stressor-Induced Inflammatory Protein
After acute stress, levels of the inflammatory protein HMGB1 increase in the hippocampus.
This protein can prime microglia to overproduce inflammatory cytokines.
Again, M. vaccae inoculation prevented the spike in HMGB1 induced by inescapable stress.
It also stopped stress from sensitizing the microglia inflammatory response to an immune stimulus.
By limiting HMGB1 release and microglial sensitization, M. vaccae appeared to shield the hippocampus from excessive inflammation.
M. vaccae Blocks Anxiety Behaviors Induced By Stress
Given its anti-inflammatory effects in the brain, the researchers tested if M. vaccae could prevent stress-induced anxiety behaviors.
They immunized adult rats with M. vaccae or saline.
A week later, they either exposed rats to inescapable stress or left them undisturbed.
24 hours afterwards, they assessed anxiety behaviors using a juvenile social exploration test.
Stressed rats spend less time interacting with a juvenile, indicating anxiety.
As expected, inescapable stress caused anxiety behaviors in saline treated rats.
However, rats inoculated with M. vaccae were protected from the anxiety-inducing effects of stress.
M. vaccae May Exert Broad Effects Across The Hippocampus
The hippocampus plays a role in both memory and emotions like anxiety.
Its dorsal region is more involved in memory while the ventral is more involved in anxiety.
The researchers found M. vaccae increased anti-inflammatory IL-4 levels throughout the hippocampus – not just in the ventral portion.
This suggests M. vaccae may exert broad effects across hippocampal functions.
Burning Questions For Future Research
This research uncovers an exciting link between a common soil microbe, inflammation in the brain hippocampus, and stress resilience.
However, many questions remain to be explored:
- How exactly does a bacterium injected in the periphery induce anti-inflammatory effects deep in the brain?
- Does inoculation with live M. vaccae confer protection against stress? Killed bacterium was used in this study.
- Can M. vaccae offer safe and effective anxiety relief in humans? Testing is still needed in humans.
- Could M. vaccae prevent stress-related disorders like PTSD and depression? These conditions are driven partly by neuroinflammation.
- What is the optimal dosing and timing of M. vaccae administration? A regimen for maximal benefits needs to be established.
- Do benefits last long-term or is repeated inoculation needed? The longevity of effects needs to be assessed.
- Could M. vaccae be used alongside therapy and medications for additive benefits? Combination approaches should be explored.
A non-infectious microbe that humans co-evolved with may offer a novel approach to shielding the brain from the damaging effects of stress and anxiety.
More research is needed, but the insights uncovered in this study are promising.
Manipulating “Old Friends” to modulate inflammation may open new paths for supporting mental health and stress resilience.
References
- Study: Immunization with M. vaccae induces an anti-inflammatory milieu in the CNS
- Authors: Matthew G. Frank et al. (2018)
