How Gut Microbiome and Blood Metabolites Drive Ossification of the Posterior Longitudinal Ligament of the Spine: A Genome-Wide Association Study Based on the East Asian Population

Objective This study explored the associations between the gut microbiome, blood metabolites, and ossification of the posterior longitudinal ligament of the spine(OPLL), and identified potential causal relationships mediated by blood metabolites. Method Using summary-level genome-wide association study (GWAS) data, including measures of the gut microbiome, blood metabolites, and OPLL, we employed a two-sample Mendelian randomization (MR) approach to identify gut microbial taxa and blood metabolites potentially associated with OPLL development. Additionally, we identified blood metabolites as mediators of the causal pathway by which the gut microbiome influences OPLL. The inverse-variance weighted (IVW) method served as the primary analytical approach in MR analysis. Sensitivity analyses including Cochran's Q test, MR-Egger regression, and MR-PRESSO were performed to assess the robustness of the results. Results MR analysis revealed unidirectional causal relationships between 20 gut microbiome taxa and OPLL. Among these, 6 taxa were positively associated with an increased risk of OPLL, while 14 taxa were negatively associated with risk. Additionally, 8 blood metabolites exhibited potential causal relationships with OPLL, with 5 showing positive and 3 showing negative associations. Mediation analysis demonstrated that 6 gut microbiome taxa influenced OPLL development through 4 intermediary metabolites. Specifically, manganese mediated the effect of Bacilli on OPLL, aspartic acid mediated the effects of Megasphaera and Prevotella oris, cystine mediated the effect of MF0036, and vitamin B2 (VB2) mediated the effects of MF0052 and MF0047 on OPLL. Conclusion This study provides evidence supporting potential causal links between specific gut microbiomes and OPLL, emphasizing the mediating role of blood metabolites.