A shot that can help cope with stress may be on the horizon, say scientists from the University of Colorado Boulder. They discovered that immunization with beneficial bacteria — probiotics — could have long-lasting anti-inflammatory effects on the brain.

Although research has only been done on animals, the results could ultimately lead to protection against post-traumatic stress disorder (PTSD) and anxiety, or new treatments for depression.

"We found that in rodents this particular bacterium, Mycobacterium vaccae, actually shifts the environment in the brain toward an anti-inflammatory state," said lead author Matthew Frank, a senior research associate in the Department of Psychology and Neuroscience.

"If you could do that in people, it could have broad implications for a number of neuroinflammatory diseases," he continued.

Anxiety, PTSD and other stress-related mental disorders affect as many as one in four people in their lifetime. Mounting research suggests that stress-induced brain inflammation can boost risk of these disorders, in part by influencing neurotransmitters like norepinephrine or dopamine that affect mood.

"There is a robust literature that shows if you induce an inflammatory immune response in people, they quickly show signs of depression and anxiety," said Frank. "Just think about how you feel when you get the flu."

Research also suggests that trauma, illness, or surgery can sensitize certain regions of the brain, setting up a hair-trigger inflammatory response to succeeding stressors which can lead to both mood disorders and cognitive decline.

"We found that Mycobacterium vaccae blocked those sensitizing effects of stress, too, creating a lasting stress-resilient phenotype in the brain," Frank said.

A previous CU Boulder study, published in the Proceedings of the National Academy of Sciences (PNAS), found that mice injected with a preparation of M. vaccae and then placed with a larger aggressive male for 19 days showed less anxiety and were less likely to suffer colitis or inflammation.

For the new study, published this week in the journal Brain, Behavior and Immunity, the researchers determined to find out what exactly M. vaccae does in the brain.

Male rats that were injected with the bacterium three times, one week apart, had significantly higher levels of the anti-inflammatory protein interleukin-4 in the hippocampus — a brain region responsible for modulating cognitive function, anxiety and fear — eight days after the final injection.

After exposure to stress, the immunized animals also showed lower levels of a stress-induced protein, or alarmin, called HMGB1, which is believed to play a role in sensitizing the brain to inflammation, and higher expression of CD200R1, a receptor key for keeping glial cells (the brain's immune cells) in an anti-inflammatory state.

As in the first study, the immunized rats showed less anxious behavior after stress.

"If you look at the field of probiotics generally, they have been shown to have strong effects in the domains of cognitive function, anxiety and fear," said Lowry. "This paper helps make sense of that by suggesting that these beneficial microbes, or signals derived from these microbes, somehow make their way to the hippocampus, inducing an anti-inflammatory state."

Lowry hopes that one day M. vaccae could be given to people at high risk of PTSD, such as soldiers, to cushion effects of stress on the brain and body.

Meanwhile, Lowry is working on a study exploring whether veterans with PTSD can benefit from an oral probiotic consisting of a different bacterial strain, Lactobacillus reuteri.

"More research is necessary, but it's possible that other strains of beneficial bacteria or probiotics may have a similar effect on the brain," he said.

Another recent study published in the medical journal Gastroenterology found probiotics to be beneficial in relieving the symptoms of depression. After six weeks, twice as many adults with irritable bowel syndrome (IBS) accompanied by depression said their depression improved when they took a specific probiotic (Bifidobacterium longum NCC3001) as compared to adults with IBS who took a placebo — 64 percent compared to 32 percent.

The results were backed by functional magnetic resonance imaging (fMRI) that showed changes in multiple areas in the brain related to mood.

Probiotics have been found to be beneficial in other areas as well. In a study from Georgia State University, mice were pretreated with a type of probiotics called Lactobacillus casei DK128, and then infected with a lethal dose of influenza. Not only did they show an immune response against the particular flu virus they were given, but they also showed immunity against other strains.

All of the pretreated mice lived, but all of the control mice, which were infected with the same lethal dose of virus, died.

An Australian study found that taking a probiotic after having a flu shot may make it work better. "Probiotics offer a relatively cheap intervention to improve vaccine efficacy and duration of protection," researchers wrote in the journal Vaccine.