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

Abstract

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.

Keywords: Gut microbiota; Mendelian randomization; Obsessive-compulsive disorder.