30 years after the scientists have pronounced the term "hygiene hypothesis" to suggest that increased exposure to microorganisms may benefit health, CU Boulder researchers have identified an anti-inflammatory fat in a soil-dwelling bacterium that may be responsible.
The discovery published Monday in the journal Psychopharmacology may at least partially explain how the bacterium [Mycobacterium vaccae] triggers stress-related disorders. It also brings the researchers one step closer to developing a microbe-based "stress vaccine."
"We think there is a special sauce that drives protective effects in this bacterium, and this fat is one of the main ingredients of the particular sauce," said senior author and integrative physiology professor Christopher Lowry.
British scientist David Strachan first proposed the controversial hygiene hypothesis in 1
"The idea is that as humans have moved away from farms and an agricultural or hunter-gathering existence to cities, we have lost contact with organisms that served to regulate our immune system and suppress inappropriate inflammation," Lowry said. "It has put us at higher risk of inflammatory disease and stress-related psychiatric disorders."
Lowry has published numerous studies showing a link between exposure to healthy bacteria and mental health. It was shown that children reared in a rural environment surrounded by animals and bacteria-laden dust grow up to have more stress-resistant immune systems and may be less at risk for mental illness than animal-free urban dwellers.
Others have shown that when a particular soil-dwelling bacterium Mycobacterium vaccae is injected into rodents, it alters the behavior of the animal in a manner similar to antidepressants and has long-lasting anti-inflammatory effects on the brain. (Studies suggest excessive inflammation increases the risk of trauma and stressor-related disorders, such as post-traumatic stress disorder.)
One Lowry-authored study, published in Proceedings of the National Academy of Sciences in 2016, showed that injections of M. vaccae prior to a stressful event could prevent a "PTSD-like" syndrome in mice, averting stress-induced colitis, and making the animals less aware when stressed again later.
"We knew it worked, but we didn't know why," Lowry said. "This new paper helps clarify it."
For the new study, Lowry and his team isolated and chemically synthesized a new 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 inner cells acted as lipid as a key in a lock, binding to a specific receptor, peroxisome proliferator-activated receptor (PPAR), and inhibiting a number of key pathways that run inflammation. They also found that when the cells were pretreated with the lipid, they were more resistant to inflammation when stimulated.
"It seems that these bacteria we developed along with have a trick on their sleeves," Lowry said. "When taken up by immune cells, they release these lipids that bind to this receptor and close the inflammatory cascade." Lowry has long imagined developing a "stress vaccine" from M. vaccae which could be given to first responders, soldiers and others in high-voltage jobs to help them avert the psychological damage to stress. "This is a major advance for us because it identifies an active component of the bacteria and receptor for this active component of the host," he said. Just knowing the mechanism of action by which M. vaccae reaps benefits could increase confidence in it as a potential therapeutic. And if further studies show that the new fat alone has therapeutic effects, the molecule could become a target for drug development, he said.
Overall, the study provides further evidence that our "old friends" have a lot to offer.  "This is only a strain of a species of a type of bacterium found in the soil, but there are millions of other strains in the soil," Lowry said. "We have just begun to see the top of the iceberg in identifying the mechanisms that they have developed to keep us healthy. It must inspire awe in all of us."
Immunization with beneficial bacteria makes the brain more stress-inhibiting, studies show.
David G. Smith et al. Identification and characterization of a novel anti-inflammatory lipid isolated from Mycobacterium vaccae, a soil-derived bacterium with immunoregulatory and stress-resistant properties, Psychopharmacology (2019). DOI: 10.1007 / s00213-019-05253-9
Healthy, stress-busting fat found hidden in dirt (2019, May 29)
May 29, 2019
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