Causal link between gut microbiota and obsessive-compulsive disorder: A two-sample Mendelian randomization analysis.

BACKGROUND

Previous studies have indicated a potential link between the gut microbiota and obsessive-compulsive disorder (OCD). However, the exact causal relationship remains uncertain. In this study, we employed a two-sample Mendelian randomization (MR) analysis to evaluate the causal connection between gut microbiota and OCD.

METHODS

We collected Genome-Wide Association Study (GWAS) summary data on gut microbiota (n = 18, 340) and OCD (n = 199, 169), using single nucleotide polymorphisms (SNPs) as the instrumental variable. SNPs with an F-statistic of <10 were deemed weak instrumental variables and subsequently excluded. The MR analysis was conducted using five methods: inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode. Heterogeneity and pleiotropy were assessed using Cochran's Q-test and MR Egger intercept test, while sensitivity analysis was performed using a leave-one-out approach.

RESULTS

The IVW analysis revealed that at the phylum level, Proteobacteria (OR = 0.545, 95%CI: 0.347-0.855, P = 0.008) served as a protective factor for OCD, whereas at the order level, Bacillales (OR = 1.327, 95%CI: 1.032-1.707, P = 0.027) was identified as a risk factor. At the family level, Ruminococcaceae (OR = 0.570, 95%CI: 0.354-0.918, P = 0.021) also acted as a protective factor. At the genus level, Bilophila (OR = 0.623, 95%CI: 0.425-0.911, P = 0.015) was a protective factor, while Eubacterium ruminantium group (OR = 1.347, 95%CI: 1.012-1.794, P = 0.041) and Lachnospiraceae UCG001 (OR = 1.384, 95%CI: 1.003-1.910, P = 0.048) were identified risk factors. Reverse MR analysis showed no significant causal relationship between OCD and the gut microbiota, with no significant heterogeneity or horizontal pleiotropy observed.

CONCLUSION

Our analysis suggested that specific gut microbiota might have a causal relationship with OCD, revealing potential intervention strategies for the prevention and treatment of this disorder.