Research linking Social Anxiety Disorder to gut microbiota health could pave the way for a novel treatment

03 Jan 2024 --- People living with Social Anxiety Disorder (SAD) have a microbiota composition different from that of healthy individuals, researchers based in Ireland found. SAD patients’ microbiota were inserted into the guts of mice, which led to an increased sensitivity to social fear and changes to stress and immune functions.

“SAD is an increasing issue for the human population, so it is vital to explore new treatments to address the condition,” says professor John F. Cryan, research lead, principal investigator at the APC Microbiome Ireland and VP for research and innovation at the University College Cork. “Discovering a link between the microbiota and the SAD condition is a significant breakthrough — the microbiota presents a potential therapeutic target.” 

“SAD has become a pertinent issue, it causes fear and anxiety in common social situations, which can be very debilitating and negatively impact quality of life,” adds co-author Dr. Nathaniel Ritz . “Our study shows that the microbiota in SAD is capable of driving symptoms characteristic of the disorder. This makes for exciting possibilities in the effort to develop therapeutics for patients suffering with SAD.” 

The study published in PNAS put forward that interkingdom — the communication between bacteria and their hosts — is a vital aspect of social fear responses and suggests the microbiome as a therapeutic target for SAD.

Impact of alterations in the bacteriome 
The researchers investigated the link between gut health and SAD using 16S rRNA sequencing performed on microbial DNA extracted from the stool samples of six patients with the disorder and matched them with those from six people not suffering from the condition.

The bacteriome beta diversity, a measure of the similarity or dissimilarity of more than one microbial community, found in the gut of the mice that received fecal microbiota transplants from SAD patients was significantly different from those received from people not affected by SAD.

The mice that received the SAD microbiota transplant were also assessed for sensitivity to sociability, social fear, anxiety-like and stress-coping behaviors through social fear conditioning, an animal model created for the study of SAD, extinction learning, which analyzed social behavior by measuring interaction time during exposure to social and non-social stimuli. 

During the time span of the six social stimuli trials, the researchers exhibited a “significant reduction” in social interaction and no difference in non-social investigatory behavior.

This provides evidence that SAD microbiota can increase sensitivity to social fear stimuli. However, general sociability, social novelty and other stress-coping behaviors were not affected.

According to experts, SAD is an increasing issue, so it is vital to explore new treatments to address the condition.Diminished stress and immune function
The research further tested the transplant’s effects on stress and immune system function by measuring the levels of the glucocorticoid stress hormone corticosterone in the plasma of the mice before and after a forced swim test.

The concentration of corticosterone was found to be “significantly reduced” among the mice with a SAD microbiota transplant, but no differences were found following the induced stress.

Differences in gut immune function in response to paradigmatic antigens were also measured, including through the harvesting of mesenteric lymph nodes, blood and the flow cytometry of immune cell populations. The findings indicate that the SAD microbiota transfer reduced the circulating stress hormone and the immunity of the mice.

The findings provide evidence that the microbiota in people living with SAD is linked to increased social fear, which in mice has been associated with impaired peripheral immune activation and neuronal oxytocin in the bed nucleus of the stria terminalis, a heterogeneous and complex limbic forebrain structure responsible for autonomic, neuroendocrine and behavioral responses. 

Emphasizing the study’s assertion that the microbiota-gut-brain axis is an “ideal target” for identifying novel therapeutics to improve symptoms in SAD, says director of APC professor Paul Ross. “At APC, we are continuing to discover how the microorganisms in our gut can affect a wide variety of human illnesses and conditions including those involved in mental health and well-being.”

“SAD can be a crippling condition, and this new discovery opens up new therapeutic avenues which take the microbiome into account with the possibility to change its composition to improve health,” he outlines. 

By Milana Nikolova