An increasing number of studies have found associations between the gut microbiota (GM) and neurological disorders. However, the causal relationship between the GM and trigeminal neuralgia (TN) remains unclear. Mendelian randomization (MR) is an effective method to link pathological changes in distant tissues, so we proposed to explore the potential causal relationships between GM and TN via MR analysis. We obtained genome-wide association study summary datasets for GM and TN from publicly available databases, respectively. After rigorous instrumental variable screening, 5 MR methods, including inverse variance weighting, MR-Egger, Weighted median, Weighted mode, and Simple mode, were used to assess the causal relationship between GM and TN. Various sensitivity analyses were also used to enhance the robustness of the results. In addition, we used multivariable MR (MVMR) to further assess the independent causal relationship between GM and TN. We initially found significant causal relationships between 5 GMs and TN, including Turicibacter (Genus), Roseburia_unclassified (Species), Acidaminococcaceae (Family), Eubacterium ruminantium group (Genus), and Bacteroides_plebeius (Species). We did not find reverse causation. In addition, MVMR suggested that only Acidaminococcaceae (Family) (odds ratio, 0.60; 95% confidence interval, 0.42-0.87; PMVMR = .006) remained a protective factor for TN. Sensitivity analyses of all negative results enhanced the robustness of our results. This study found the causal relationship between GM and TN, which may provide potential new insights to the gut-brain axis and contribute to the understanding of the TN. However, further experiments are needed to clarify the protective effect of GM on TN and its mechanism.
