Abstract
BACKGROUND: Despite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear. METHODS: Gut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships. RESULTS: We identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29-2.69); p = 8.63E-04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47-0.93); p = 1.81E-02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50-0.97); p = 3.00E-02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00-1.51); p = 4.94E-02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35-0.88); p = 1.14E-02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota. CONCLUSION: Our MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.