Causal link between gut microbiota and obsessive-compulsive disorder: A two-sample Mendelian randomization analysis (Mar 2025) Causation 

Michael Harrop

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https://www.psypost.org/gut-bacteria-may-play-a-causal-role-in-obsessive-compulsive-disorder-study-suggests/
https://www.sciencedirect.com/science/article/abs/pii/S0165032725003167

Highlights​

  • Novel Gut Microbes-OCD Link: Provided evidences of causal ties between specific gut microbiota and OCD.
  • Implications for OCD Management: Proposed microbiome-targeted therapies for OCD prevention and treatment.
  • Public Health Significance: Highlighted urgent need to study gut-brain mechanisms in rising OCD cases.

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.
 
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