Around thirty years ago, scientists coined the term “hygiene hypothesis” which suggests that increased exposure to microorganisms could benefit health. Today, researchers from the University of Colorado Boulder found evidence to back up their hypothesis. They have identified an anti-inflammatory fat in a soil-dwelling bacterium that may be responsible.
The bacterium, Mycobacterium vaccae (M. vaccae), has the ability to quell stress-related disorders because it contains a fatty acid called 10(Z)-hexadecenoic acid. This fatty acid interacts with immune cells to inhibit pathways that drive inflammation, and in so doing, it increases resilience to stress. The discovery has been published in the journal Psychopharmacology.
The researchers say it has brought them one step closer to developing a microbe-based “stress vaccine.” Senior author and Integrative Physiology Professor Christopher Lowry, said: “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.”
Theory Refined
It was back in 1989 when British scientist David Strachan first proposed the controversial “hygiene hypothesis”. At the time, there was no evidence to back up his theory but he proposed it anyway. Strachan suggested that in our modern, sterile world, the lack of exposure to microorganisms in childhood was leading to impaired immune systems and higher rates of allergies and asthma.
Since Strachan expressed this idea, researchers have been searching for clues and answers to validate the theory. They have succeeded in refining the theory which now suggests that it is not lack of exposure to disease-causing germs at play, but rather to “old friends” – beneficial microbes in soil and the environment. They have also come to find that it isn’t only our immune system that is impacted, but our mental health as well.
“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’s Studies
The link between exposure to healthy bacteria and mental health has been the topic of numerous studies published by Lowry. Of these, one showed 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. Others showed that when M. vaccae (a particular bacterium) is injected into rodents, it alters the animals’ behavior in a way similar to that of antidepressants and even has long-lasting anti-inflammatory effects on the brain. As other different studies have suggested, exaggerated inflammation boosts the risk of trauma- and stressor-related disorders, such as posttraumatic stress disorder (PTSD).
The possibility of a “stress vaccine” is made evident through one of these studies on mice. The researchers injected the mice with M. vaccae prior to a stressful event and it was able to prevent a “PTSD-like” syndrome in mice, fending off stress-induced colitis and making the animals act less anxious when stressed again later. This specific study was published in the Proceedings of the National Academy of Sciences in 2017. “We knew it worked, but we didn’t know why,” Lowry said. “This new paper helps clarify that.”
To find out why, Lowry and his team then identified, isolated, and chemically synthesized a novel lipid, or fatty acid, called 10(Z)-hexadecenoic acid found in M. vaccae. Next, they used next-generation sequencing techniques to study how it interacted with macrophages, or immune cells when the cells were stimulated. What they found was that once inside cells, the lipid acted like a key in a lock, binding to a specific receptor, peroxisome proliferator-activated receptor (PPAR), and inhibiting a host of key pathways which drive inflammation. Furthermore, when cells were pre-treated with the lipid they were more resistant to inflammation when stimulated.
Lowry said:
It seems that these bacteria we co-evolved with have a trick up their sleeve. When they get taken up by immune cells, they release these lipids that bind to this receptor and shut off the inflammatory cascade. 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.
Stress Vaccine
Throughout all these studies, Lowry has envisioned developing a “stress vaccine” from M. vaccae. He sees it as being beneficial for people in high-stress jobs, like first responders and soldiers, to help them fend off the psychological damage of stress.
“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.”
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