Abstract:

Objective To explore the potential causal relationship between the gut microbiota and the risk of head trauma. Methods We conducted a two-sample Mendelian randomization （MR） analysis to explore the potential causal relationship between gut microbiota and head injury， utilizing summary statistics from European ancestry cohorts. The inverse-variance weighted （IVW） method was employed as the primary analytical approach. A two-stage discovery-validation design was adopted. To guarantee reliability， significant findings from a training cohort were validated in an independent testing cohort， and then a meta-analysis was carried out. Moreover， multivariable Mendelian randomization （MVMR） was performed to evaluate independent effects， and reverse MR analysis was used to examine the direction of causality. Results In the discovery phase （training cohort）， six bacterial taxa were identified as potentially associated with the risk of head injury. Crucially， the risk effect of the Eubacterium nodatum group was successfully replicated in the independent validation cohort （IVW OR： 1.001， P = 0.012）. The meta-analysis of both cohorts further supported suggestive associations for four taxa. Notably， all the observed effect sizes were small （ORs close to 1）， which warrants a cautious interpretation of the clinical relevance. Conclusions Our study offers preliminary genetic evidence indicating that specific gut microbial taxa might have a causal association with the risk of head injury. These findings imply that dysbiosis could affect injury susceptibility， possibly via neurocognitive or neuromuscular pathways. Nevertheless， considering the small effect sizes and partial replication， these results should be regarded as exploratory and necessitate further validation in larger， multi-ethnic cohorts.

Key words: gut microbiota, head injury, causal effects, Mendelian analysis, meta analysis