Causal relationship between gut microbiota and pyogenic arthritis: a two-sample Mendelian randomization study

<b>Introduction.</b> Accumulating evidence indicates a significant association between gut microbiota and the risk of developing pyogenic arthritis (PA). However, their causal relationship has yet to be elucidated.<b>Hypothesis.</b> The gut microbiota is causally associated with the risk of PA.<b>Aim.</b> The Mendelian randomization (MR) methodology was employed to assess the potential causal effects of gut microbiota on the susceptibility to PA.<b>Methodology.</b> A two-sample MR study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (<i>n</i>=13,266) conducted by the MiBioGen consortium. The summary statistics of PA were obtained from the R11 release data provided by the FinnGen consortium (2,441 cases and 2,87,796 controls). Inverse-variance weighted (IVW) model, weighted median estimator model, weighted model-based method and MR-Egger regression (MER) model were used to examine the causal association between gut microbiota and PA. To assess the heterogeneity and pleiotropic effects of the identified instrumental variables (IVs), we utilized several analytical methods, including the leave-one-out sensitivity analysis, the MR Pleiotropy Residual Sum and Outlier test and Cochran's Q test.<b>Results.</b> Utilizing the IVW method, we identified six bacterial traits that were negatively correlated with PA: <i>Eubacterium eligens</i> group [OR: 0.6057; 95 % confidence interval (CI): 0.4525 to 0.8107; <i>P</i>=0.0007], <i>Barnesiella</i> (OR: 0.7456; 95 % CI: 0.5760 to 0.9651; <i>P</i>=0.0258), <i>Coprococcus2</i> (OR: 0.7257; 95 % CI: 0.5352 to 0.9840; <i>P</i>=0.0391), <i>Ruminococcaceae</i> UCG005 (OR: 0.7562; 95 % CI: 0.5920 to 0.9660; <i>P</i>=0.0252), <i>E. oxidoreducens</i> group (OR: 0.7311; 95 % CI: 0.5547 to 0.9637; <i>P</i>=0.0262) and <i>Lachnospiraceae FCS020</i> group (OR: 0.7825; 95 % CI: 0.6135 to 0.9981; <i>P</i>=0.0482), respectively. On the contrary, four bacterial traits were positively correlated with PA: <i>Adlercreutzia</i> (OR 1.3210, 95 % CI 1.0181-1.7141, <i>P</i>=0.0362), <i>Holdemania</i> (OR 1.2239, 95 % CI 1.0013-1.4960, <i>P</i>=0.0485), <i>Anaerostipes</i> (OR 1.3614, 95 % CI 1.0189-1.8191, <i>P</i>=0.0369) and <i>Butyricimonas</i> (OR 1.2627, 95 % CI 1.0016-1.5921, <i>P</i>=0.0484), respectively. No significant heterogeneity among IVs or evidence of horizontal pleiotropy was detected.<b>Conclusion.</b> Our research demonstrates a potential causal link between various gut microbiota and the risk of PA. Further research is imperative to elucidate the mechanisms by which gut microbiota influence the pathogenesis of PA.