Study spotlights link between gut microbiota and social anxiety disorder

04-Jan-2024 - Last updated on 04-Jan-2024 at 11:31 GMT

New research suggests that gut microbiota play a role in the heightened social fear response tied to social anxiety disorder (SAD), representing a potential therapeutic target for reducing the growing behavioural issue of social fear.

The researchers from APC Microbiome Ireland and University College Cork (UCC) used faecal microbiota transplants (FMT) to transplant microbiota from SAD or healthy control (HC) patients to mice before subjecting the mice to a range of behavioural assessments and an analysis of faecal samples, ileal tissue and hormonal levels.

The resulting data indicated that FMT from a SAD donor negatively affects gut bacterial colonisation and leads to increased sensitivity to social fear stimuli.

“This is an important step in causally implicating the gut microbiome in regulating the brain circuits underpinning social fear," Prof John Cryan, vice president for research and innovation at UCC and lead author on the study, told NutraIngredients. “Moving forward the goal will be to target the microbiome with psychobiotic-based probiotics or prebiotics or whole diet approaches that will reverse some of the alterations seen.”

Researcher Dr Nathaniel Ritz who worked on the study while at APC, commented on the importance of finding effective treatment for this psychiatric disorder: “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.

“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 gut and social anxiety

Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function.

The research team behind the current study recently showed that patients with SAD have a different microbiota composition than age-matched healthy controls (HC).

Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses.

Study details

In the recent study, following antibiotic depletion of the microbiota, 72 mice received specified donor FMT (SAD or HC microbiota) and were tested for social fear, sociability, social cognition and stress-coping behaviours, as well as gastrointestinal transit and motility.

The authors reported that murine recipient bacteriome beta diversity was significantly altered between SAD and HC groups measured at the end of the study. There were three bacterial species that were differentially abundant in the SAD and HC groups at the end of the study—Bacteroides nordii, Bacteroides cellulosiyticus and Phocaeicola massiliensi.

According to the authors, this alteration in bacteriome community composition confirms that the FMT from SAD and HC donors led to differential microbiotas recolonizing and engrafting following antibiotic microbiota depletion.

Social fear, sociability, anxiety-like, and stress-coping behaviours were assessed using elevated plus maze, three-chamber test, carmine red gastrointestinal transit and motility test, social fear conditioning and forced swim test.

Results showed a significant reduction in social interaction over the six social stimuli trials (W(1) = 3.239, P < 0.05) and no difference in non-social investigatory behaviour.

The study stated that the witnessed reduction in social fear extinction rate provides evidence that the SAD microbiota is capable of increasing sensitivity to social fear stimuli.

The glucocorticoid stress hormone corticosterone was measured in plasma of mice before and after the forced swim test.

Following euthanasia, small intestinal ileal tissue was explanted and stimulated with lipopolysaccharide (LPS), concanavalin A (ConA), T cell receptor clusters of differentiation 3 and 28 (CD3/CD28) or vehicle (buffer) to assess gut immune function in response to paradigmatic antigens between groups. These data indicate that the SAD microbiota transfer reduced circulating stress hormone and peripheral immunity.

“Taken together, our findings provide novel evidence that the microbiota in individuals with SAD can generate increased social fear that is associated with impaired peripheral immune activation and neuronal oxytocin within the BNST in mice," the study concluded. "This suggests that the microbiota can play a causal role in heightened social fear responses in the disorder. Moving forward, the microbiota–gut–brain axis is an ideal target for identifying novel therapeutics to improve symptoms in SAD."

Director of APC Prof Paul Ross added: “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 wellbeing. Social Anxiety Disorder 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.”

Source: Neuroscience
doi: doi.org/10.1073/pnas.2308706120
“Social anxiety disorder-associated gut microbiota increases social fear”
Authors: Cryan, J.F. et al.