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03-05-2024

Breakthrough discovery: Social anxiety can be targeted in the gut 

A groundbreaking study conducted by researchers at the University College Cork and the APC Microbiome Ireland has revealed  a potentially transformative insight into the treatment of social anxiety, a condition affecting approximately 15 million adults in the United States alone. 

The study’s innovative approach involved transplanting gut microbes from humans with social anxiety disorder (SAD) into mice, leading to the manifestation of social phobia behaviors in the animals just ten days post-transplantation. 

This novel finding not only highlights the intricate link between the gut and mental health but also underscores the gut microbiota‘s critical role in modulating stress responses, as evidenced by altered levels of corticosterone, a key hormone in stress regulation.

Targeting social anxiety in the gut

The implications of this discovery are profound, suggesting that the gut–brain axis is an ideal target for identifying novel therapeutics to improve symptoms’ of social anxiety in humans. 

This insight adds a significant layer to the growing body of research highlighting the microbiota-gut-brain connection, positing that a range of neurological conditions, including anxiety, depression, autism, and others, could potentially be mitigated by addressing gut-related imbalances.

Fear and anxiety in social situations 

“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,” said lead author Nathaniel Ritz, who conducted the study while at APC.

“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.”

Gut microbes and social anxiety

Crucially, the study noted marked disruptions in the immune systems of the mice post-transplant, indicative of the role inflammatory molecules play in the gut-brain communication pathway. 

This aspect of the research was an extension of an existing exploration into the relationship between gut microbes and social anxiety in humans, leveraging microbial samples from volunteers participating in the study.

How the research was conducted 

The methodological approach adopted by the scientists involved 12 microbiome samples, derived from fecal samples, from individuals diagnosed with social anxiety disorder (SAD) and those without such a diagnosis. 

Prior to inclusion, participants were screened to ensure they were not on any psychiatric medications or nutritional supplements that could influence their microbiome composition. 

To prepare the mice for the study, they were administered a cocktail of antibiotics to effectively reset their gut microbiota, creating a blank slate for the human microbiome samples to be implanted.

Establishing new microbiomes 

This meticulous process involved splitting each participant’s sample six ways and administering it to six different mice, totaling 72 mice – half receiving transplants from SAD individuals and the other half from those without SAD. 

The transplantation was executed through a feeding tube over three consecutive days, ensuring the successful establishment of the new microbiomes.

Prolonged social fear responses 

Subsequent evaluations of the mice across a spectrum of behavioral and physiological parameters revealed stark differences in their responses, particularly in tests measuring social fear

Mice receiving microbiome transplants from SAD individuals exhibited significantly prolonged social fear responses, a hallmark of social anxiety, despite no discernible differences in sociability between the two groups of mice. 

This phenomenon mirrors the human experience of social anxiety, where the desire for social interaction is often overshadowed by overwhelming anxiety.

Social anxiety linked to distinct gut microbial profile

In addition to behavioral changes, the study uncovered significant microbiome variations between the two mouse groups, affirming the distinct gut microbial profiles between SAD-afflicted individuals and those without the disorder. 

Notably, the mice implanted with SAD microbiomes exhibited pronounced changes in their brains, including altered levels of oxytocin – often dubbed the “love hormone” – which plays a pivotal role in social bonding and stress regulation.

New hope for millions of social anxiety sufferers

These findings not only illuminate the causative role of the gut microbiota in social anxiety but also open up new avenues for therapeutic intervention targeting the gut–brain axis. By leveraging this axis, the researchers hope to identify and develop innovative treatments that can effectively ameliorate the symptoms of social anxiety disorder, offering hope to millions grappling with this debilitating condition.

“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,” concluded APC director Paul Ross.

The study is published in the journal Proceedings of the National Academy of Sciences.

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