A study conducted in Sweden discovered that transplanting the gut microbiota from individuals with social anxiety disorder into mice made these mice more sensitive to social fear. While the mice maintained normal behavior in a variety of other non-social behavioral tests, researchers identified several biochemical changes. This research was published in the journal Neuroscience.
Social anxiety disorder, also known as social phobia, is a mental health condition characterized by an intense fear of social situations, where individuals feel excessively self-conscious, judged, or embarrassed, leading to avoidance of social interactions. Research suggests that abnormalities in the brain’s serotonin and dopamine systems (networks of neurons that use neurotransmitters serotonin and dopamine to regulate various functions), as well as hyperactivity in the amygdala (a region involved in fear and emotional processing), may contribute to the development of social anxiety.
The recent uncovering of the microbiota-gut-brain axis, a sophisticated bidirectional communication network between the gut microbiota and the brain, has garnered attention towards the potential influence of gut microorganisms on various psychological and mental health issues. This axis includes neural, endocrine, immune, and metabolic pathways through which gut microbiota can impact brain development, mood, cognition, and stress responses. Given its bidirectional nature, the brain can also affect the composition of the gut microbiota.
A recent study has shown that gut microbiota composition of individuals suffering from social anxiety disorder differs from that of healthy individuals. However, it remained unknown whether these differences might be caused by the disorder or whether they might have a causal role in developing this disorder.
To better study the role of gut microbiota in social anxiety disorder, Nathaniel L. Ritz and his colleagues conducted a study on mice in which they examined whether gut microbiota might play a causal role in the development of social anxiety disorder. To do that, they transplanted gut microbiota from individuals suffering from social anxiety disorder and healthy individuals into mice and observed the changes that developed.
The study involved 6 participants diagnosed with social anxiety disorder and 6 healthy adults without any psychiatric illness history. Those with social anxiety disorder were already part of a study investigating the specificities of gut microbiota in individuals with the disorder. Healthy participants were recruited through University College Cork and provided stool samples for transplantation into mice.
The recipients of the transplantations were 72 male mice, 8 weeks old at the beginning of the study. After their acquisition, the mice were given 2 weeks to adjust to their new environment, maintained on a 12-hour dark-light cycle, and given unrestricted access to standard mouse food and water.
Following the acclimatization period, the researchers began treating the mice with a potent cocktail of antibiotics in their drinking water, composed of ampicillin, vancomycin, imipenem, and neomycin. This regimen eradicated the mice’s native gut microbiota, preparing them for the human microbiota transplants. Each mouse received gut microbiota from a randomly selected human participant.
The human participants’ stool samples were diluted, filtered to eliminate large particles, and then administered directly into the mice’s guts via oral gavage over three consecutive days. Of these, 36 mice received microbiota from participants with social anxiety disorder, and the remaining 36 received it from healthy participants.
Ten days post-procedure, the researchers conducted a series of behavioral tests and collected stool samples from the mice before and after the transplant, alongside conducting comprehensive biochemical analyses.
The results indicated differences in the gut microbiota between the two groups of mice, with variations in the abundance of three bacterial species – Bacteroides nordii, Bacteroides cellulosiyticus, and Phocaeicola massiliensi.
Behavioral tests showed that mice who received gut microbiota from participants with social anxiety disorder had reduced social interactions across six trials. However, their non-social behaviors did not change. This led the researchers to conclude that sensitivity to social fear of these mice was increased.
Further analysis showed that these mice had reduced levels of the hormone corticosterone. Corticosterone is a steroid hormone produced by the adrenal cortex, primarily involved in regulating stress responses, energy metabolism, immune reactions, and electrolyte balance in the body.
The mice that received gut microbiota from participants with social anxiety disorder also showed lower levels of oxytocin in specific regions of the brain (the bed nucleus of the stria terminalis) and lower activity of genes related to oxytocin in other brain regions (the medial amygdala and prefrontal cortex). These changes are linked to higher levels of social fear.
“Taken together, our findings provide novel evidence that the microbiota in individuals with SAD [social anxiety disorder] can generate increased social fear that is associated with impaired peripheral immune activation and neuronal oxytocin within the BNST [the bed nucleus of the stria terminalis] in mice. 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,” the study authors concluded.
The study sheds light on the role gut microbiota play in social anxiety disorder. However, it should be noted that the study was performed on mice with depleted gut microbiota. Results on humans might not be the same.
The paper, “Social anxiety disorder-associated gut microbiota increases social fear,” was authored by Nathaniel L. Ritz, Marta Brocka, Mary I. Butler, Caitlin S. M. Cowan, Camila Barrera-Bugueño, Christopher J. R. Turkingtona, Lorraine A. Draper, Thomaz F. S. Bastiaanssen, Valentine Turpin, Lorena Morales, David Campos, Cassandra E. Gheorghe, Anna Ratsika, Virat Sharma, Anna V. Golubeva, Maria R. Aburto, Andrey N. Shkoporov, Gerard M. Moloney, Colin Hill, Gerard Clarke, David A. Slattery, Timothy G. Dinan, and John F. Cryan.