Gut microbiome diversity mediates the association between right dorsolateral prefrontal cortex and anxiety level

Despite the fast growing interest in the impact of microbiome-gut-brain interaction on regulating emotional behavior in animals, the underlying mechanisms on how brain anatomy together with gut microbiotic condition jointly influence emotional state in healthy human volunteers remain largely unknown and hypothetic. Here, high-resolution structural magnetic resonance imaging data, stool samples, and psychological assessment results on anxiety level were collected from 61 healthy adults. Voxel-based morphometry was used to assess gray matter (GM) volumes, whereas 16s rRNA gene sequencing was used for bacterial classification. Correlation and mediation analysis were conducted to quantify the relationships among regional GM volume, gut microbiome diversity, and anxiety level. We observed that anxiety level was negatively correlated with GM volume in the right dorsolateral prefrontal cortex and alpha diversity index of gut microbiome. Additional mediation analysis revealed the indirect effect of dorsolateral prefrontal cortex GM volume on anxiety level via gut microbiome diversity. Our findings provide potential evidence of the microbiome-gut-brain interactions and their association with anxiety, highlighting gut microbiome diversity as a mediator that influences the relationship between brain morphometry and anxiety level.