A bacterium that lives in the dirt has been used to develop a vaccine that lowers the response to stress in mice. In the future, a similar drug injected into humans might protect us against PTSD-like symptoms, just like vaccines today protect you against the flu. Now, a new study has uncovered the molecular mechanisms that enable this dampening response, bringing us closer to a drug that might protect humans against stress.

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Last year, researchers at the University of Colorado Boulder, led by Cristopher Lowry, found that exposure to a soil-based bacterium called Mycobacterium vaccae made mice less reactful to stressful situations. The mouse models also had lower levels of stress-induced proteins and showed less anxious behaviors when exposed to stress just eight days after the last injection, according to the 2008 study.

These findings are extremely appealing. PTSD is caused by exposure to a traumatic event or frightening experiences such as sexual assault, war, natural disaster, accidents or the threat of death to oneself or a loved one. Post-traumatic stress disorder is a long-lasting consequence of incredibly traumatic events that overwhelm a person’s ability to cope. About 1 in 30 Americans will develop PTSD during their lifetimes, and countless others are affected by depression, which is another stress-related psychiatric disorder.

“We envision use of immunizations with heat-killed mycobacteria for treatment of stress-related psychiatric disorders, in conjunction with cognitive behavioral therapy and treatment as usual,” Lowry said during a statement in 2018.

Now, a new study, Lowry and colleagues have revisited the topic — this time, the researchers looked for the molecular mechanisms that might explain the observed effect. In their new study, the team identified and isolated a lipid in the bacterium, called 10(Z)-hexadecenoic acid, that apparently tunes down the flight-or-fight response in mammals.

“We knew it worked, but we didn’t know why,” said Lowry. “This new paper helps clarify that.”

The lipid binds to receptors inside immune cells, blocking certain chemicals from causing inflammation. In the lab, the researchers also synthesized this lipid. When it was used to coat cells, the researchers found that these cells were resistant to the stimulation of an inflammatory response. So, the vaccine offered protection against stress-induced inflammation and altered the animals’ behavior similarly to antidepressants.

“We think there is a special sauce driving the protective effects in this bacterium, and this fat is one of the main ingredients in that special sauce,” said Lowry, who is an Integrative Physiology Professor.

Christopher Lowry. Credit: CU Boulder.

Previously, Lowry published numerous studies that correlated healthy bacteria with mental health. One study showed that children raised in rural areas, where they were surrounded by farm animals and dust, grew up to have a more resilient immune system and were at lower risk of mental illness compared to pet-free city dwellers.

Lowry has long envisioned developing a “stress vaccine” from M. vaccae, which could be given to first responders, soldiers and others in high-stress jobs to help them fend off the psychological damage of stress.

“This is a huge step forward for us because it identifies an active component of the bacteria and the receptor for this active component in the host,” he said.

This is just the beginning. In the future, who knows what other kinds of beneficial bacteria scientists might be able to uncover.

“This is just one strain of one species of one type of bacterium that is found in the soil but there are millions of other strains in soils,” Lowry said. “We are just beginning to see the tip of the iceberg in terms of identifying the mechanisms through which they have evolved to keep us healthy. It should inspire awe in all of us.”

The findings were reported in the journal Psychopharmacology.