Causal Relationship Between Gut Microbiota and Non-Suicidal Self-Injury: A Two-Sample Mendelian Randomization Study.

Area of Science:

• Genetics and Microbiology
• Psychiatry and Behavioral Science

Background:

• Non-Suicidal Self-Injury (NSSI) is a complex behavior with significant public health implications.
• The gut microbiota's role in mental health is increasingly recognized, but its specific connection to NSSI remains underexplored.

Purpose of the Study:

• To investigate the potential causal relationship between gut microbiota composition and NSSI.
• To explore bidirectional effects using a two-sample Mendelian Randomization (MR) approach.
• To identify specific gut microbial taxa associated with NSSI risk and protection for potential therapeutic targets.

Main Methods:

• Utilized a two-sample Mendelian Randomization (MR) design with genome-wide association study (GWAS) data.
• Employed Inverse Variance Weighted (IVW) and MR-robust adjusted profile score (MR-RAPS) for forward MR (gut microbiota to NSSI).
• Conducted reverse MR (NSSI to gut microbiota) and comprehensive sensitivity analyses (MR-Egger, weighted median, heterogeneity, leave-one-out) to ensure result validity.

Main Results:

• Forward MR identified 38 gut microbial genera associated with NSSI, including Dorea (risk-enhancing) and Escherichia Shigella (protective).
• Specific taxa like Lachnospiraceae UCG001 and Paraprevotella showed associations with self-injurious behavior.
• Reverse MR revealed significant links between NSSI and microbial taxa such as Prevotella9 (inflammation) and Faecalibacterium (protective effects).

Conclusions:

• Established a complex, bidirectional relationship between gut microbiota and NSSI.
• Identified specific gut bacteria with both risk-increasing and protective associations with NSSI.
• Suggests gut microbiota as a potential modifiable target for future therapeutic interventions for NSSI.