Fecal Microbiota Transplantation From Patients With Social Anxiety Disorder Is Associated With General Anxiety-Like Behavior and Gut Microbiota Alterations in Mice.

PURPOSE: Growing evidence implicates gut microbiota dysbiosis in social anxiety disorder (SAD), yet direct causal evidence remains limited. This study investigated whether fecal microbiota transplantation (FMT) from individuals with SAD was associated with general anxiety-like behaviors and accompanying gut microbial and predicted metabolic alterations in mice.

METHODS: Fecal samples were collected from five patients diagnosed with SAD and five matched healthy controls and transplanted into antibiotic-treated mice. Anxiety-like behaviors were evaluated using the open-field test (OFT) and elevated-plus maze test (EPMT). Gut microbiota composition was assessed by 16S rRNA gene sequencing, microbial functional potential was inferred using PICRUSt2, and plasma tryptophan-pathway metabolites were quantified.

RESULTS: Mice receiving SAD microbiota (SAD group) showed general anxiety-like behaviors, characterized by more time spent in the periphery of the OFT and fewer entries and less time in the open arms of the EPMT compared to mice receiving healthy control microbiota (control group). Although α-diversity did not differ significantly, β-diversity was distinct between groups. The SAD group showed enrichment of Bacteroidota/Bacteroidales-related bacteria (e.g., Muribaculum), whereas the control group had higher abundance of butyrate producers (e.g., Butyricimonas). Functional prediction indicated lower predicted abundance of selected DNA-repair and biosynthetic pathways in the SAD group. Plasma tryptophan levels were nominally lower in the SAD group.

CONCLUSIONS: These findings suggest that specific gut microbiota alterations and predicted functional pathway changes in individuals with SAD may be associated with anxiety-related behavioral phenotypes, supporting the gut microbiome as a potential contributing factor to the pathophysiology of SAD.