Causal Relationships between Gut Microbiota and Depression/Anxiety Disorders: A Two-Sample Mendelian Randomization Study

Abstract

Background Evidence shows that the composition of the gut microbiota (GM) is associated with depression and anxiety disorders. However, the causal relationship between them remains controversial. Methods To investigate the potential causal relationship between the gut microbiota and depression/anxiety disorders and to identify specific bacterial taxa, we conducted a two-sample Mendelian randomization (MR) analysis on the gut microbiome implicated in depression and anxiety disorders. We incorporated summary data from a genome-wide association study (GWAS) of the microbiome derived from 7,738 individuals participating in the Dutch Microbiome Project (DMP) as our exposure variable. Concurrently, the GWAS of depression and anxiety disorders was employed as our outcome variable. The principal estimates were procured using the inverse-variance weighted (IVW) test complemented by four robust methods: MR Egger, weighted median, simple mode, and weighted mode. In addition, we performed comprehensive sensitivity and directionality analyses. Results The results showed that 5 bacterial taxa were positively correlated with depression, 6 were negatively correlated; 5 were positively correlated with anxiety disorders, and 11 were negatively correlated. Conclusions This study provides new insights into the connection between the gut microbiota and the pathogenesis of depression and anxiety disorders and offers new perspectives for the diagnosis and treatment of these disorders.