New research published in the Journal of Affective Disorders provides evidence that the gut microbiome may play a functional role in the development of social anxiety disorder. The study found that transplanting gut bacteria from adolescents with social anxiety into newborn rats induced anxiety-like behaviors and altered brain chemistry in the animals. These findings suggest that specific alterations in the gut-brain axis could contribute to the pathology of social anxiety during adolescence.
Social anxiety disorder is a prevalent mental health condition characterized by an intense and persistent fear of social situations and negative evaluation by others. While psychological therapies and medications exist, they are not effective for every patient. This has led scientists to investigate alternative biological systems that might contribute to the disorder.
The gut-brain axis has emerged as a significant area of interest. This term refers to the bidirectional communication network between the gastrointestinal tract and the central nervous system. Previous studies have linked gut microbiota differences to various psychiatric conditions, including depression and autism spectrum disorder.
While earlier observations have indicated that people with social anxiety might have different gut bacteria than healthy individuals, it has been unclear if these microbial differences caused the symptoms or were merely a consequence of the disorder. A team of researchers led by Jinghong Chen of Shanghai Jiao Tong University School of Medicine sought to move beyond simple correlation by using an experimental model to test for causality. They focused on adolescence because this is a critical period for brain development and is often when social anxiety symptoms first manifest.
“Our study was driven by both a pressing clinical reality and a compelling scientific inspiration,” explained co-author Junyu Lai, a member of Chen’s research laboratory.
“First, the real-world problem: Social anxiety disorder is a prevalent and often disabling condition that typically emerges during adolescence. As clinicians and researchers, we have long noticed that current first-line treatments—such as pharmacotherapy and psychotherapy—often show limited effectiveness and do not work for every child. We urgently need new therapeutic avenues that are safer and more accessible.”
“Second, we drew significant inspiration from the ‘gut-brain axis,’ particularly the high-impact research linking gut microbiota to the pathogenesis of autism spectrum disorder,” Lai explained. “Seeing how profound the gut’s influence is in autism, we asked ourselves: Could a similar disruption in the gut microbiome be driving social anxiety disorder?”
“This question motivated us to explore whether social anxiety disorder patients exhibit a distinct gut microbial environment. Our hope is that by confirming this link, we can pave the way for a new generation of treatments—interventions focused on maintaining gut health. We believe this could offer a more economical, safer, and sustainable long-term solution for managing social anxiety disorder symptoms, ultimately improving the quality of life for young patients.”
To conduct the study, the research team recruited 40 adolescents diagnosed with social anxiety disorder from the Shanghai Mental Health Center and local communities. They also enrolled 32 healthy control participants who were matched for age and gender. The researchers imposed strict inclusion criteria to ensure the results were not influenced by other factors.
All participants with social anxiety were experiencing their first episode of the disorder, had no other psychiatric comorbidities, and had never taken psychiatric medication. The team collected fecal samples from all participants to analyze the genetic composition of their gut bacteria.
The researchers used a fecal microbiota transplantation method to test the effects of these bacteria on brain development. They pooled the fecal samples from the anxiety group and the healthy group into two distinct composites.
They then administered these microbiota suspensions to newborn rats. The treatment began on the first day of life and continued daily until the rats reached late adolescence. This method differs from many similar studies that use adult rats treated with antibiotics to deplete their natural bacteria. The authors chose to colonize newborn rats to mimic the natural developmental process and avoid the potential side effects of high-dose antibiotics, which can independently cause anxiety in rodents.
Once the rats reached adolescence, the researchers evaluated them using a series of behavioral tests. They used an open field test to assess general anxiety and locomotor activity. In this test, anxious animals typically stick to the walls and avoid the center of the arena.
The researchers also employed an elevated plus maze, which consists of open and enclosed arms raised above the ground. Rats with lower anxiety levels typically explore the open arms, while anxious rats prefer the safety of the enclosed spaces. Finally, the team used a three-chamber social test to measure sociability and social novelty preference. This test observes how much time a rat spends interacting with a stranger rat compared to an empty cage or a familiar rat.
The analysis of the human samples revealed that the gut microbiota composition in adolescents with social anxiety differed from that of the healthy controls. While the overall diversity of the bacterial community was similar, specific bacterial genera showed significant variance. The anxiety group had higher levels of a genus called Prevotella and lower levels of Parasutterella.
“Unlike studies on autism, where the gut microbiota composition often shows drastic structural shifts, the changes we observed in social anxiety patients appeared relatively subtle,” Lai told PsyPost. “This initially raised concerns within our team about whether these microbial differences were sufficient to drive the pathology. However, the results from our animal models provided a compelling and encouraging turning point.”
The behavioral results in the rats mirrored the clinical picture seen in humans. The rats that received the microbiota from the social anxiety patients exhibited distinct anxiety-like behaviors. In the open field test, these rats spent less time exploring the center zone compared to the control group.
Similarly, in the elevated plus maze, the anxiety-colonized rats ventured into the open arms less frequently. In the social testing, these rats demonstrated a reduced preference for social novelty. While they still interacted with other rats, they did not show the typical preference for investigating a new, unfamiliar rat over a rat they had already met. This indicates a potential deficit in social processing.
Following the behavioral tests, the researchers analyzed the medial prefrontal cortex (MFC) of the rats. This brain region is essential for regulating emotions and processing social information.
The analysis revealed distinct metabolic changes in the brains of the rats colonized with anxiety-associated bacteria. The researchers identified alterations in several metabolites, including lower levels of beta-carotene and changes in amino acids such as threonine and aspartic acid. The researchers noted that the decline in Parasutterella in the gut was associated with changes in cholesterol and bile acid metabolism. These metabolic shifts in the brain were correlated with the anxiety-like behaviors observed during testing.
“The most significant takeaway is that social anxiety disorder appears to have a distinct biological footprint in the gut,” Lai explained. “Our study confirmed that the gut microbiota composition in adolescents with social anxiety disorder is different from that of healthy peers.”
“More importantly, we found that this is not just a correlation. When we transplanted this ‘anxiety-associated microbiota’ into rats, the animals began to exhibit anxiety-like behaviors and social deficits, mirroring the human symptoms. We even observed specific metabolic changes in the MFC, a brain region critical for social processing. This provides compelling evidence that the gut-brain axis plays a functional role in the pathology of social anxiety.”
There are some limitations to this study that affect how the results should be interpreted. The human participants were all Han Chinese adolescents, meaning the findings may not generalize to adults or people of other ethnicities. The study identified changes in the bacterial community as a whole but did not pinpoint the specific bacterial strains or metabolites responsible for the behavioral effects. Additionally, the researchers did not measure markers of the immune system or the stress response system, which are likely involved in transmitting signals from the gut to the brain.
“I want to be very clear about what this means—and what it doesn’t mean yet,” Lai said. “We haven’t found a ‘magic pill’ yet: We have not yet pinpointed the specific bacteria or metabolites responsible for these changes. We know the community has an effect, but we don’t know the exact ‘key players.’”
“Our study focused specifically on treatment-naïve Han Chinese adolescents to ensure a clean experimental baseline. We need further research to confirm if these findings apply to adults, other ethnicities, or broader populations. The picture is still incomplete: We have not yet fully mapped how this interacts with other body systems, such as the immune system or the HPA (stress) axis.”
Future research will need to address these gaps by examining larger and more diverse populations. The authors plan to investigate the specific bacterial species that drive these changes and explore the intermediate pathways, such as immune signaling. While the results are promising for understanding the biology of social anxiety, they do not yet provide a basis for clinical treatments.
“Our current study is just the beginning, and acknowledging our limitations points us directly toward our future research directions,” Lai explained. “We have mapped out three key steps.”
“First, we aim to move from ‘community’ to ‘specificity’. In this study, we observed the effects of the whole gut microbiota community. However, as noted in our limitations, we have not yet pinpointed the specific bacterial taxa or the precise metabolites responsible for the observed effects. Our next step is to isolate and identify the specific ‘key players’—whether it is a particular bacterial strain or a specific metabolic byproduct—that directly drives the metabolic changes we saw in the mPFC.”
“Second, we plan to map the full ‘communication highway’ between the gut and the brain,” Lai said. “While we confirmed the endpoint (mPFC metabolic changes) and the starting point (gut dysbiosis), our current study did not comprehensively measure the intermediate pathways, such as the immune system or the HPA (hypothalamic-pituitary-adrenal) axis. In future studies, we intend to integrate these systemic factors to fully understand how the gut signals reach the brain—whether through immune activation, hormonal pathways, or direct neural routes.”
“Finally, we need to test the generalizability of our findings. Our current cohort consisted specifically of treatment-naïve Han Chinese adolescents. To ensure our findings are universally applicable, we plan to expand our research to larger, more diverse populations, including different age groups and ethnicities. This will help us determine if the gut-brain mechanisms we discovered are consistent across all SAD patients or specific to certain developmental stages.”
The study, “Gut microbiota from adolescents with social anxiety disorder is associated with behavioral alterations and metabolic changes in the medial prefrontal cortex,” was authored by Junyu Lai, Beibei Yang, Peijun Ju, Ying Sun, Xiujia Sun, Wenhong Cheng, and Jinghong Chen.
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