Gut microbiota from adolescents with social anxiety disorder is associated with behavioral alterations and metabolic changes in the medial prefrontal cortex

Abstract

Background: Social anxiety disorder (SAD) is a prevalent and burdensome neuropsychiatric disorder characterised by pronounced and persistent fear and anxiety in social situations. While evidence links gut microbiota to neuropsychiatric disorders, its role in SAD remains poorly understood.

Aim: In this study, we aimed to investigate the potential involvement of gut microbiota in SAD pathophysiology through fecal microbiota transplantation.

Method: We collected demographic data and fecal samples from 40 first-episode, comorbidity-free, and drug-naive adolescent patients with SAD, along with 32 demographically matched healthy controls. Fecal samples underwent 16S rDNA amplicon sequencing and were pooled for transplantation into neonatal rats from postnatal day 1 through late adolescence. Recipient rats were evaluated with behavioral tests, microbiota detection, and non-targeted metabolomics of the medial prefrontal cortex.

Result: Patients with SAD displayed alterations in gut microbiota composition. Rats colonized with SAD-associated microbiota exhibited anxiety-like behaviors and reduced social novelty preference, alongside microbial profiles partially overlapping with those of patients. These behavioral changes were correlated with microbiota differences, and distinct metabolic alterations were detected in the medial prefrontal cortex of SAD-colonized rats.

Conclusion: Gut microbiota from adolescents with SAD is associated with behavioral and metabolic alterations in a rodent model, suggesting a potential role of the gut-brain axis in SAD. Further studies are warranted to establish causality and elucidate underlying mechanisms.

Keywords: Fecal transplant; Microbiome; Microbiota-gut-brain axis; Psychiatry; Social anxiety disorder; Social phobia.