Cleanliness may be next to godliness. But, it turns out, being a deity is pretty nerve-wracking.

Growing up in meticulously sanitized conditions, devoid of the “old friends” germs and parasites that have coevolved with us and help train our immune systems, leaves us more prone to a host of health issues. These include inflammatory bowel disease, allergies, asthma, and autoimmune disorders, scientists have found. Prevalence of these health issues has soared in the squeaky-clean developed world. But that’s not all. This well-established hypothesis—the hygiene hypothesis—may also explain rises in certain mental health issues, according to a growing number of studies.

The same inflammation and haywire immune responses that may be explained by the hygiene hypothesis have also been linked to depression, anxiety, and stress disorders, such as post-traumatic stress disorder (PTSD). Studies have found that high levels of inflammation increase the risk of developing depression, for instance, and PTSD is associated with pro-inflammatory signals and reduced regulatory T cells—cells that quell immune responses, including inflammation.

Immune signals—including errant ones—can alter brain signals, the brain’s release of hormones, and the neural circuitry for mood, researchers have found. While the findings highlight the importance of our microbial communities to our health, they also offer hints on how to treat such mental health problems.

Step aside, probiotic yogurts

With the new appreciation for the microbiome and its roles, researchers are eagerly chasing ideas for harnessing the power of microbes and boosting health—most notably by trying to reconcile with bygone microbes. To this end, entrepreneurs have developed probiotic foods and bacterial-laden body washes—with dubious success. But now, scientists are tackling the mental health connections and have pinned down some promising early results.

By injecting mice with dead batches of a once-common gut microbe, researchers show that they can manipulate the rodent’s immune systems, alter gene regulation in their brains, and reduce stressed-out and anxious behaviors. While the study, published in the Proceedings of the National Academy of Sciences, was only conducted in a small pack of mice, the findings hint at future therapeutics that could tap microbial community members to block psychiatric disorders.

“These data support a strategy of “reintroducing” humans to their old friends to promote optimal health and wellness,” the authors conclude.

For the study, the researchers chose heat-killed Mycobacterium vaccae, an abundant soil-dweller that feasts on dead or decaying organic matter and is known to spur immune responses in mice.

Compared with control mice that didn’t receive a vaccine of M. vaccae, the injected mice showed less anxious and submissive behavior in a stress test. The test involved tossing males into a cramped cage with a dominant male and monitoring their behavior. While 95.7 percent of control mice showed at least one submissive behavior in the first hour, such as standing upright, avoidance, and flight behaviors, only 65.3 percent of the vaccinated mice did. Additionally, the vaccinated mice scored higher on dominance indexes, which accounts for chasing and fighting behavior.

When the researchers glimpsed into the brains of the mice, they found that the vaccinated rodents had turned on genes involved with stress-coping strategies. And, while the control mice generally developed stress-induced colitis—inflammation of the colon— during the month-long test, the vaccinated mice did not.

Lastly, when the researchers gave the vaccinated mice an antibody that throws off the activity of regulatory T cells—those inflammation-calming cells—the protective effects of the vaccine were wiped away.

For now, it’s too early to extrapolate the specific findings to human health. But the study suggests that reintroducing humans to the microbes of their dirty days of yore may be able to improve mental health. “Restoring exposure to these old friends through immunization or other routes may decrease inflammation-associated disease vulnerability in modern urban societies,” the authors write.

Proceedings of the National Academy of Sciences, 2016. DOI: 10.1073/pnas.1600324113 (About DOIs).