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Stalking the dirt vaccine

Stalking the dirt vaccine

Can good bacteria make the brain more stress-resilient? Christopher Lowry has dedicated his career to finding out


Christopher Lowry was a precocious 6-year-old, fond of playing in the dirt near his home in rural Wyoming, when researchers 8,000 miles away made a discovery that would end up shaping his career.

The year was 1971. British scientists had noticed that people living near Lake Kyoga in Uganda responded much better to certain vaccines than those elsewhere did. They suspected something in the environment was at play, and when they investigated, they discovered an intriguing orange slime鈥攍ater identified as Mycobacterium vaccae鈥攕tretching across the shoreline.

Lowry

Christopher Lowry in his lab. CU Photo by Glenn Asakawa. Photo at top of the page by Xan Griffin, Unsplash.

鈥淚t appeared that this microorganism living in the soil had powerful immune-regulating properties that were somehow making the vaccines work better,鈥 says Lowry, now an integrative physiology professor at the University of Colorado Boulder and pioneer in the study of how bacteria impact mental health.

In the 18 years since he first heard the story of M. vaccae, Lowry has published a series of ground-breaking papers suggesting that exposure to it, and other beneficial bugs in our midst, may have a profound impact on not only our physical health, but also our mental wellbeing.

The more we depart from the rural environments in which we evolved and the more sterile we make our surroundings, the more we risk missing out on the gifts of these microbial 鈥渙ld friends,鈥 he warns. In the meantime, he鈥檚 forging ahead with studies aimed at someday harnessing those gifts, in the form of probiotic treatments for mental illness鈥攐r even a 鈥渟tress immunization.鈥 

鈥淎s human societies have migrated to urban environments, we have lost touch with a host of bacterial species that have the capacity for immunoregulation, and we believe this is helping to fuel an epidemic of inflammatory disease,鈥 says Lowry. 鈥淚 want to know: What are the impacts on mental health? And, more importantly, what new interventions can we present to prevent things like anxiety disorders, PTSD and depression?鈥

How do bugs talk to the brain?

Lowry was a research fellow at the University of Bristol in the UK in the early 2000s when he began to hear stories about M. vaccae. In the decades since that discovery at the lake, researchers have tried using it as an immune-boosting adjunct to various vaccines, with limited success. 

But one trial testing it in lung cancer patients yielded a curious result:

While those injected with the bacterium didn鈥檛 live longer, they reported improved quality of life, including mental health. 

鈥淭his suggested that there was some mechanism through which these injections of M. vaccae were affecting the brain,鈥 explains Lowry, who quickly set out to find an answer.

Headlines about the 'dirt antidepressant' abounded. But many of his peers were skeptical. Now, they're not so skeptical.

In April 2007, he published a study in the journal Neuroscience showing that a heat-killed preparation of M. vaccae,when injected into mice, activated neurons in the brain that produce the feel-good chemical serotonin and altered their behavior in a way similar to that of antidepressants.

Headlines about the 鈥渄irt antidepressant鈥 abounded. 

But many of his peers were skeptical.

鈥淪ome people commented that it must have been an April Fool鈥檚 joke,鈥 he recalls.

It would be another nine years of toiling away in the lab before Lowry published the follow-up paper in Proceedings of the National Academy of Sciences(PNAS), showing that injections of M. vaccae prior to a stressful event could actually help mice become more stress-resilient, fending off conditions like stress-induced colitis and making them act less anxious and fearful when later stressed.

In short, Lowry says, M. vaccae could prevent a 鈥淧TSD-like鈥 syndrome in mice. 

Since then, he鈥檚 published a flurry of studies with collaborators around the globe, adding weight to the notion that good bacteria can be good for the mood.

One study of 40 healthy men, published in the April 2018 issue of PNAS with researchers at the University of Ulm in Germany, 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.

Another paper, published with Dr. Matt Frank, a senior research associate in the department of psychology and neuroscience, found that in animal models, M. vaccae has a long-lasting anti-inflammatory effect on the brain. That鈥檚 important, explains Frank, because stress-induced brain inflammation has been shown to boost risk of anxiety and mood disorders, in part by impacting mood-influencing neurotransmitters like norepinephrine or dopamine.

鈥淚f you could reduce brain inflammation in people, it could have broad implications for a number of neuroinflammatory diseases,鈥 explains Frank.

In 2016, the  named Lowry鈥檚 research among the 鈥淭op 10鈥 advancements in mental health research鈥攁n illustration that the scientific community is coming around.

鈥淭here is a growing recognition that the microbiome can impact health in general and, more specifically, mental health,鈥 said Dr. Jeffrey Borenstein, president of the foundation.  鈥淒r. Lowry鈥檚 work can potentially be a game-changer in our understanding of this and could ultimately lead to new treatments.鈥 

Lowry notes that, while more research is needed, some evidence already suggests that probiotic supplements can have an anti-inflammatory effect, boost cognitive function and possibly alleviate anxiety.

While M. vaccae has been the focus of his research, other microorganisms also hold promise.

He鈥檚 collaborating with the Department of Veterans Affairs on a clinical trial looking at whether Lactobacillus reuteri can improve physiological and psychological responses to stressful situations in veterans with PTSD.

Someday, he imagines an M. vaccae-based 鈥渟tress immunization鈥 could be given to soldiers, nurses, first responders or people in other high-stress jobs to make their brains and bodies more resilient.

鈥淚 do not want to promote this as a panacea,鈥 he emphasizes, noting that many other factors influence whether someone develops a mental illness. 鈥淏ut I do think this could play an important role.鈥

In the meantime, he makes a point of exposing his two children, 6 and 8, to a healthy dose of dirt, via a front yard vegetable garden and frequent camping trips, like he was exposed to as a child. He encourages his friends and colleagues to do the same.

Only now, they鈥檙e not so skeptical.

鈥淚t went from being this novel, turn-your-world upside down concept to something that doesn鈥檛 even surprise people anymore,鈥 he says. 鈥淚t鈥檚 exciting to see so many people interested in our relationship with the microbial world.鈥