CREATURE COMFORT

Dirt has a microbiome, and it may double as an antidepressant

No one would blame you for not wanting your body to be infested with creatures from your garden. But maybe you should rethink your position.

Your garden has its own microbiome, and research suggests it’s good for you. Our health depends on the flourishing microbiome in our guts—and on how much of the natural world’s microbiome we let infiltrate.

Lately, thanks to modern life, we don’t let in a lot. But in a string of pioneering studies, scientists are beginning to look at what would happen if we literally inject microbes from the soil into our bodies, reintroducing us to the ancient relationship between bacteria and human. So far, the results have been uplifting—to both the scientists and the subjects they study.

In 2004, Mary O’Brien, an oncologist at the Royal Marsden Hospital in London, published a paper with unexpected results: She injected lung cancer patients with a common, harmless soil bacteria, Mycobacterium vaccae, to see if it could prolong their life. M. vaccae had some success in earlier trials where it was tested for its abilities to fight drug-resistant pulmonary tuberculosis and boost immune system response. O’Brien thought maybe the bacteria could help her patients’ immune systems beat back the cancer in their lungs. It failed.

Only, it succeeded elsewhere: the bacteria injection “significantly improved patient quality of life,” O’Brien wrote in the paper detailing the findings. Her patients were happier, expressed more vitality, and better cognitive functioning—in short, it reduced the emotional toll of advanced cancer.

Garden Microbiome 1
(Neslihan Gunaydin/Unsplash)

A few years later, Christopher Lowry, a neuroscientist at the University of Bristol, injected M. vaccae into mice and subjected them to a series of stress tests. The ones inoculated with the bacteria showed far less stressed behavior than their untreated counterparts—in fact, they acted as if they were on antidepressants. In a 2007 paper published in the journal Neuroscience, Lowry and his team wrote that the bacteria activated groups of neurons in the mouse brains responsible for producing serotonin—a neurotransmitter that, when impaired, can cause depression. Even more intriguingly, the neurons that lit up were also known to be related to immune response, suggesting an intimate connection between the immune system and emotional health.

The world of biomedical research has already fallen in love with the promising realm of the human gut microbiome. A body of emerging evidence tells us the millions of microbes in our digestive tract influence our immune systems, our smells, our mood, and possibly even our attractiveness to mosquitoes—and to other people. But M. vaccae expands this thinking to the microbiome of the pile of mulch in your backyard.

There’s now pretty good evidence to draw at least an outline of a conclusion: Breathing in, playing in, and digging in dirt may be good for your health. Our modern, sterilized life in sealed-off office buildings and homes are likely not. Researchers have already found clear evidence that childhood exposure to outdoor microbes is linked to a more robust immune system; for example, Bavarian farm children who spent time in family animal stables and drank farm milk had drastically lower rates of asthma and allergies throughout their lives than their neighbors who did not.

But the rest of us, not raised on farms, may be missing out on that sort of protection. Some counterbalance, like spending time in a garden, might change that.

Tomato plant
(Dan Gold/Unsplash)

One reason dirt is so good for us might be M. vaccae, which, after Lowry’s 2007 paper, emerged on the scene as a sort of celebrity bacterium. Papers published since have described feeding mice M. vaccae-laced peanut butter sandwiches, and watching them race through challenging mazes far faster than their counterparts, suggesting the bacteria gave them a significant brain boost, in addition to apparently elevating their mood. That paper also demonstrated that eating the bacteria, instead of injecting it, could still give the mice those benefits. Which suggests eating trace amounts of it from garden vegetables, or breathing it in, may be too, for humans.

Good news: you can get the stuff anywhere. Step out to your yard, or the neighborhood park, and you’re likely to encounter some M. vaccae. The bacteria lives naturally in soil, though what factors make soil more or less abundant with M. vaccae are still being investigated (a team led by Lowry is in the process of inspecting 300 soil samples from across the US and Europe for the tiny creatures). Have a garden? Even better. Grow some food: “A three to four leaf spinach plant has over 800 species of bacteria inside it,” Lowry says; eating straight from the garden might be one route to more M. vaccae in your life.

Don’t have a garden, and not a fan of getting dirt under your nails? M. vaccae may be in your municipal water supply, too: Lowry, together with University of Colorado-Boulder microbiologist Noah Fierer, have embarked on an endeavor they call The Showerhead Microbiome Project, which is exactly what it sounds like: They’re soliciting samples of water from people’s showerheads across the US and Europe, to see whether and how many mycobacterium—M. vaccae included—live there. Of course, every showerhead microbiome will be different; they hope to assess what factors (like the type of tap water supplied by your city, or what type of showerhead you use) make it more or less hospitable to different bacterial colonies.

Old as dirt

Imagine, for a moment, if the word “parasite” didn’t elicit grimaces. What if “fungus” wasn’t gross, and “bacteria” sounded more like, say, the word “electrolytes” does to us now?

Our ancestors lived for centuries with a host of ancient parasites, fungi, and bacteria (including M. vaccae) and didn’t mind at all. “We’ve forgotten that these were beneficial,” says Emeran Mayer, a gastroenterologist and neuroscientist at the University of California-Los Angeles and author of The Mind-Gut Connection. “They might have caused an initial infection, but could then live in symbiosis with us,” Mayer says. Many of these organisms evolved alongside humans, and likely the entire line of mammals we descended from, too. “The benefit we got was that we had a much more clever immune system that didn’t attack our own selves.”

That’s according to the “old friends” theory developed by University College London microbiologist Graham Rook in the early 2000s when the “hygiene hypothesis” didn’t seem to be able to explain why autoimmune conditions like allergic asthma were on the rise even in so-called “unhygienic” cities. The hygiene hypothesis pinned skyrocketing allergic and autoimmune disease rates on just our modern obsession with cleanliness; the “old friends” hypothesis casts a wider net of blame, implicating modern medicine’s aggressive antibiotic use, pasteurized food, indoor living, and anything else that is eradicating these “old friends” from our systems.

Take Helicobacter pylori, for example. Roughly half the population carries H. pylori in their guts. But after scientists found aggressive strains of the bacteria played a role in gastritis, ulcers, and stomach tumors in the 1980s, eradication became a priority. Since the 1950s, clean drinking water had already driven H. pylori rates down in richer countries, but now antibiotics were loosed on the bacteria, too, in sick patients. But as Scientific American noted, researchers began noticing children without H. pylori in their stomachs had higher rates of skin allergies, while other research found being a host for the bacteria provided some protection against gluten intolerance. H. pylori, it seems, is a very old friend; scientists are studying whether re-infecting mice with milder strains of the bacteria might offer any immune protection.

Plant pots
(Annie Spratt/Unsplash)

It’s in your head, too

If you want to understand how an ancient soil bacteria might ward off anxiety and depression, then you need to take the “old friends” theory about modern immune dysfunction, and combine it with another biomedical concept researchers are just beginning to understand: The immune system and the brain are intimately connected. And in turn, scientists are finding more and more proof that depression and other mental health conditions are associated with prolonged inflammation—a sure sign of an immune system problem.

Up until relatively recently, immune responses and brain activity were considered functions of separate systems. But “at least half the brain cells are not nerve cells, but are immune-like cells,” Mayer says, referring to “glial” cells, which are now understood to communicate intimately with our central nervous systems. “It’s quite clear now that anything going on with the immune system can correspond with the brain.”

The portion of American adults taking antidepressants nearly doubled between 1999 and 2012, rising from 6.8% of the population to 13%. Depression among teens, especially, is on the rise, by multiple measures: for example, teens in the 2010s were twice as likely to see a professional about mental health issues and significantly more likely to experience classic depression symptoms than their 1980s counterparts.

Could the trend in depression rates be related to the rise in immune conditions and the chronic inflammation that comes with them? Possibly. The science is in its infancy, but when Christopher Lowry, the neuroscientist, injected mice with M. vaccae and watched some of these immune-linked neurons light up, he knew he was on to something.

In 2016, Lowry, now at UC-Boulder, again injected mice with M. vaccae, and subjected them to a series of stressful scenarios to see just how effective bacteria was at reducing anxiety.

If you’re wondering how you can tell a lab mouse is anxious, picture yourself paralyzed by fear of making a risky decision, and then perhaps not making one at all. Mice do this too; their anxiety is measured as a conflict between “approach and avoidance” when researchers place them in unpredictable situations. “We like to think of it as unpredictable situations where you have unpredictable outcomes. So if you’re a teenager and you want to ask someone out to prom, you can anticipate different outcomes,” Lowry says. Will your desired date say yes or no? “Those situations create these anxiety states, where there’s uncertainty about outcomes.” That uncertainty may cause a more anxiety-prone teenager to freeze, and not ask their crush out to prom at all.

Mice can’t do the prom test, but they sure do get anxious about mazes, especially if only half the maze has protective walls. In Lowry’s test, the other half, or “arm,” of the maze was a sort of elevated gangplank; instead of being confined by walls, they were hemmed in by the threat of falling off on either side. “Mice naturally avoid open spaces where they’re vulnerable. On the other hand, they naturally like to explore new spaces because they find new rewards,” Lowry says. “Something that makes a mouse more anxious will cause them spend more time in the closed arms,” forgoing the potential reward of exploring an open space. But the mice injected with M. vaccae readily explored the open parts of the maze, apparently unstressed. The bacteria also reduced the colon inflammation typically seen in stressed-out mice.

In another case, the researchers placed individual mice in the same enclosure as a dominant, alpha-male mouse, which usually triggers a classic dominant-subordinate relationship immediately. “The subordinate position is an uncomfortable place to be,” Lowry says. But the mice treated with M. vaccae seemed to not notice. They showed 50% less of the typical flight-or-freeze behaviors the same scenario triggered in untreated mice. And they showed less submissive behaviors for weeks after treatment.

“These were dramatic shifts. We consider it a more proactive response to stress, rather than passive,” Lowry says. That distinction is important: “We know in humans, PTSD is a passive response to stress.”

Lowry wants to know if this humble soil bacteria be a key for treating PTSD, a sometimes treatment-resistant condition. Together with Lisa Brenner, the director of Veteran Affairs Rocky Mountain Mental Illness Research Education and Clinical Center in Denver, he has begun research with veterans suffering from PTSD and mild traumatic brain injury.

“We’re using a probiotic we know has immunoregulatory properties similar to M. vaccae. We’re also exploring pursuing clinical trials for PTSD and depression.” It’s a long way off, but these are first steps to seeing if a “vaccine” of sorts for PTSD and depression is possible.

For now, the research seems to at the very least to bolster what gardeners have been saying for centuries: Gardening is great therapy.

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