In a new study, researchers from the University of Colorado Boulder have identified an anti-inflammatory fat in a soil-dwelling bacterium, called Mycobacterium vaccae, that may have the ability to ward off stress and anxiety.
The finding, published in the journal Psychopharmacology, may help explain why exposure to microorganisms seem to benefit health, a phenomenon known as the “hygiene hypothesis.” It also brings the researchers one step closer to developing a microbe-based “stress vaccine.”
“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 senior author and Integrative Physiology Professor Christopher Lowry.
British scientist David Strachan first proposed the controversial “hygiene hypothesis” in 1989, suggesting that in our modern, sterile world, lack of exposure to microorganisms in childhood was leading to impaired immune systems and higher rates of allergies and asthma.
Researchers have since refined that theory, suggesting that it is not the lack of exposure to disease-causing germs at play, but rather the reduced exposure to “old friends” like beneficial microbes in soil and the environment, and that mental health is also impacted.
“The idea is that as humans have moved away from farms and an agricultural or hunter-gatherer existence into cities, we have lost contact with organisms that served to regulate our immune system and suppress inappropriate inflammation,” said Lowry, who prefers the phrases “old friends hypothesis” or “farm effect.”
“That has put us at higher risk for inflammatory disease and stress-related psychiatric disorders.”
Lowry has published numerous studies demonstrating a link between exposure to healthy bacteria and mental health. One of these studies shows that children raised in a rural environment, surrounded by animals and bacteria-laden dust, grow up to have more stress-resilient immune systems and may be at lower risk of mental illness than pet-free city dwellers.
Other studies have shown that when Mycobacterium vaccae is injected into rodents, it alters the animals’ behavior in a way similar to that of antidepressants and has long-lasting anti-inflammatory effects on the brain.
Research suggests that exaggerated inflammation boosts the risk of trauma- and stressor-related disorders, such as posttraumatic stress disorder (PTSD).
One recent Lowry-authored study, published in the journal Proceedings of the National Academy of Sciences in 2017, showed that injections of M. vaccae prior to a stressful event could prevent a “PTSD-like” syndrome in mice, fending off stress-induced colitis and making the animals act less anxious when stressed again later.
“We knew it worked, but we didn’t know why,” said Lowry. “This new paper helps clarify that.”
For the new study, the research team identified, isolated and chemically synthesized a novel lipid, or fatty acid, called 10(Z)-hexadecenoic acid found in Mycobacterium vaccae and used next-generation sequencing techniques to study how it interacted with macrophages, or immune cells, when the cells were stimulated.
They discovered that inside cells, the fatty acid acted like a key in a lock, binding to a specific receptor and inhibiting a host of key pathways which drive inflammation. They also discovered that when cells were pre-treated with the fatty acid they were more resistant to inflammation when stimulated.
“It seems that these bacteria we co-evolved with have a trick up their sleeve,” said Lowry. “When they get taken up by immune cells, they release these lipids that bind to this receptor and shut off the inflammatory cascade.”
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.