Your Gut Microbes May Influence How You Handle Stress

The gut microbiome – the ecosystem of tiny organisms found inside all of us – has become fertile new territory for the study of a range of psychiatric disorders and neurological diseases.

Research has shown that the brain and gut are in constant communication and that changes in the microbiome are linked to mood and mental health. Now, a study published this month in Natural mental health finds distinct biological signatures in the microbiomes of people who are highly resilient to stressful events.

“It was really astonishing how precisely these patterns emerged,” says Arpana Church, a neuroscientist at UCLA’s Goodman-Luskin Microbiome Center, who led the new study.

This research provides a starting point for future human studies that some researchers believe could eventually lead to treatments. It may also pave the way for biomarkers in the microbiome that help guide decisions about treatment and mental health.

Resilience linked to anti-inflammatory microbes

For their analysis, Church and his team separated 116 adults without a mental health diagnosis into two groups based on their score on a psychological resilience scale.

Then they sifted through a huge amount of data collected from brain imaging, stool samples and psychological questionnaires and fed it into a machine learning model to find patterns.

This analysis of gene activity, metabolites and other data highlighted several key associations in the high resilience group. In the brain, there was an increase in characteristics linked to better emotion regulation and better cognition.

“Think about that front part of your brain that feels like the brakes,” says Church. “The very resilient individuals had really effective brakes, and less of this hyper-stressed response.»

Next, they delved into the microbiome, looking not only at the abundance of different microorganisms, but also at their genetic activity to see what they were doing.

Two major trends emerged in people who were more resilient to stress: their microbiome activity was linked to reduced inflammation and improved gut barrier integrity.

Research has shown that patients with various psychiatric conditions have a balance of gut bacteria including more of certain pro-inflammatory bacteria and fewer bacteria with anti-inflammatory effects.

Church notes that the intestinal barrier absorbs nutrients and prevents toxins and pathogens from entering the bloodstream. When this becomes more permeable, or “leaky,” the resulting inflammation acts as a stress signal to the brain that all is not well.

Microbes that “talk” to our nervous system

The new study is part of a growing body of work on the brain-gut connection.

“I was really excited to see this come to fruition in a pretty large human cohort,” says Thomaz Bastiaanssen, a bioinformatician who studies the gut microbiome and mood at the University of Amsterdam Medical Center.

In recent years, he says, scientists have established that there is a strong “bidirectional relationship” between the gut and the brain. Much of this information is based on preclinical laboratory studies using animal models, as well as human observational studies and in vitro work.

“All of this points to about four ways in which the microbiome communicates with the host,” says Bastiaanssen.

Besides the immune system, there is the vagus nerve which functions like a highway, running from the brain to the gut and directly interfacing with the microbiome.

This intestinal microbiota also “communicates” with the central nervous system by secreting neurotransmitters, such as serotonin and dopamine (around 90% of serotonin is produced in the intestine and around 50% of dopamine).

Additionally, the microbiome can produce short-chain fatty acids that help maintain the integrity of the intestinal barrier and exert, among other things, an anti-inflammatory effect on the brain.

Last year, Foster and his team discovered that a community of bacteria linked to the production of these short-chain fatty acids was reduced in people with depression and high anxiety.

In recent years, other observational studies have strengthened the evidence linking the gut microbiome and mental health in humans.

For example, large studies by researchers in the Netherlands have shown that microbiomes containing less bacterial diversity may be predictive of depression, and that the presence of more or less certain bacteria linked to the synthesis of neurotransmitters and acids Short-chain fat may be essential.

Foster called the UCLA study “new” because it took a holistic view of the brain-gut microbiome and its potential role in resilience.

She notes that the analysis revealed a link between anxiety and the microbiome, which is already a well-established area of ​​research. More than a decade ago, Foster and others showed this link in laboratory experiments on “germ-free” mice and anxiety.

In the context of stress, scientists have found that even short-term exposure to stress can lead to alterations in the microbiome, and that changing the composition of the microbiome could make some mice more resilient to stress.

Probiotic treatments against stress? Not yet

Increasing efforts are being made to direct this research toward concrete treatments, using diets and prebiotic and probiotic supplements. But Bastiaanssen says the complexity of the microbiome requires a different approach than that typically used in pharmaceutical development, which tends to focus on finding a single molecule or drug.

He says it’s like trying to grow a forest in a desert by planting a few seeds.

“Obviously it’s not going to work,” he says, “because there’s no supporting ecosystem.”

He says the microbiome field is still in its infancy.

“We established a link in the microbiome, gut-brain axis. We have really strong evidence,” he says. “The next question we need to understand is: How exactly does this work?

He notes that there is promising evidence from small human studies that have shown that targeting the microbiome with certain diets (in one case, a diet high in fermented foods) can reduce inflammation.

Another trial, by Bastiaanssen and a team at the University of Cork, found that a diet focused on vegetables and foods known to influence the microbiota could reduce perceived stress.

While these efforts are entirely “valid,” Foster says the power of these studies is that they can lead to the discovery of biomarkers that can help guide decisions about how and on whom to use existing treatments. will be the best candidate.

“Can I measure something in your microbiome, maybe in your blood and maybe in your brain, to determine if you’re depressed? ” she says. “Should I give you an antidepressant…or neurostimulation?” Should I get cognitive behavioral therapy or tell you to exercise? »

This could be the value of a holistic marker that can be measured in your microbiome, she says. And she thinks it could become an effective tool for clinical care over the next decade.

For his part, Church envisages, hypothetically, one day exploit this area of ​​research to “design a mixture of probiotics that could help alleviate stress” and prevent the onset of certain diseases.

“The biggest issue is that we need more studies that are actually going to test these products in human trials,” she says. She acknowledges that there are all kinds of unsubstantiated claims about improving the microbiome. For now, she tells people the data isn’t yet strong enough to know which treatment to try.

“There’s not really one that’s really been tested,” she said, “I say come back to me in a year or so and I’ll let you know.”