Scientists have found that social anxiety lives in a person’s gut, which could lead to new treatments that affects 15 million US adults,
Researchers at Ireland’s University College Cork transplanted gut microbes from a human with the disorder into mice, which showed social phobia behaviors 10 days post implantation.
The team found the animal subjects also had reduced levels of the hormone corticosterone, which is involved with regulation of energy, immune reactions and stress responses.
The findings, according to researchers, has suggested that ‘the microbiota–gut– brain axis is an ideal target for identifying novel therapeutics to improve symptoms’ to improve social anxiety in humans.
Social anxiety, depression, and other conditions are linked to the gut microbiome in ways that scientists are just beginning to unravel
These results add to a growing body of research that shows a complex link between the intestinal tract and the brain, suggesting that anxiety, depression, autism, and other brain conditions could be treated at least in part by addressing issues that start in the gut.
Importantly, immune system markers indicated that the mice had disrupted immune systems after the transplant, suggesting that this so-called ‘gut-brain axis’ involves inflammatory molecules that can travel from the gut to the brain.
This study was an offshoot of an existing research experiment that the scientists were doing with people.
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The gut microbe samples came from people who had volunteered for a study that was looking into the relationship between gut microbes and social anxiety in people.
So while they had the samples, they tried something strange.
The scientists behind the study started with 12 microbiome samples – fecal samples – from six people with a formal diagnosis of social anxiety disorder (SAD) and six people without social anxiety
Before they could be included in the study, all of the participants had to confirm that they weren’t on any psychiatric medications or any nutritional supplements that could affect their microbiome.
Mice were prepared for the study by feeding them a mix of four different antibiotic drugs for a week, ‘to deplete the resident microbiota.’
In other words, they were given an intestinal clean slate.
Then, each participants’ poop donation was split up six ways and implanted into six different mice, for a total of 72 mice – 36 receiving transplants from people with SAD and 36 receiving transplants from people without.
Scientists implanted the new microbiome into each mouse’s gut via a feeding tube for three days in a row, to ensure that the new microbiome took hold.
The gut is connected to the brain via the vagus nerve. Scientists suspect that some people with untreatable depression or anxiety may respond to treatments that target their microbiome instead of their brain
Ten days after they started the treatment, the mice were run through a series of tests to examine a range of functions including sociability, general anxiety, gut function, depression, and fear.
On most tests, the two groups of mice performed similarly.
But there was one test where the group that had received the transplant from people with SAD performed significantly worse: a test of social fear.
In this experiment, the scientists induced fear in the mice, fear triggered by social cues, and then measured how long it takes for it to go away.
Even though the SAD group took much longer for their social fear to diminish, there was no difference in sociability between the two groups.
So the researchers concluded that what they were observing was the mouse version of social anxiety.
In people, too, social anxiety may be there even when a person has the desire to be sociable. That is what can make the condition so distressing.
Inflammatory molecules can pass between the gut and the brain, so scientists suspect that the immune system plays a role in the so-called gut-brain axis
Tests of the mouse microbiomes found that they were significantly different between the two groups, confirming that the two groups of people – those with and without SAD – had significantly different gut microbes.
These mice stayed otherwise healthy, but in addition to their newfound social anxiety, they also showed some unique changes in their brains.
Specifically, the brain region called the bed nucleus of the stria terminalis had tamped down levels of the so-called ‘love hormone’ oxytocin, which is important for bonding between parent and child as well as between individuals in both social and romantic settings.
This brain region is important to anxiety and stress responses, and the mice with SAD transplants showed serious changes.
Additionally, the medial amygdala and prefrontal cortex both had lowered expression of genes linked to oxytocin in the SAD transplant mice. These brain areas are involved in fear and personality, respectively.
So clearly, the changes to their microbiomes had triggered some significant differences in behavior.
It isn’t totally clear how one change led to the other, but the scientists suspect that it has to do with the immune system: Markers of inflammation were increased in the SAD transplant mice, and these markers can cross the blood-brain barrier.
The study was published in the journal Proceedings of the National Academy of Sciences.
While the study did not identify a treatment, it did open up a door to developing one in the future.
‘This suggests that the microbiota can play a causal role in heightened social fear responses in the disorder,’ wrote the study’s authors.
‘Moving forward, the microbiota–gut–brain axis is an ideal target for identifying novel therapeutics to improve symptoms in SAD.’
