The causality between gut microbiota and ankylosing spondylitis: Insights from a bidirectional two-sample Mendelian randomization analysis

Background: The association between gut microbiota and ankylosing spondylitis (AS) has been reported in the literature; however, whether the two are correlative is unclear.Methods: Single nucleotide polymorphisms associated with the gut microbiome composition and AS (968 AS cases and 336 191 controls) were obtained from published genome-wide association studies in this two-sample Mendelian randomization (MR) study. The causal relationship between gut microbiota and AS was estimated using the inverse-variance weighted method, and the robustness of our findings was confirmed through a comprehensive series of sensitivity analyses.Results: Anaerotruncus (OR = 0.9984, 95% CI, 0.9968-0.9999, p = .0405) and Ruminococcaceae UCG002 (OR = 0.9989, 95% CI, 0.9979-0.9999, p = .0375) were protective against AS. Defluviitaleaceae (OR = 1.0015, 95% CI, 1.0005-1.0025, p = .0048), Butyricicoccus (OR = 1.0016, 95% CI, 1.0001-1.0032, p = .0429), Coprococcus 3 (OR = 1.0016, 95% CI, 1.0000-1.0032, p = .0463), and Defluviitaleaceae UCG011 (OR = 1.0016, 95% CI, 1.0005-1.0027, p = .0041) exhibited significant positive correlations with heightened susceptibility to AS. Reverse MR revealed that AS does not affect the gut microbial composition.Conclusion: Our study has established a genetically-based causal relationship between gut microbiota and AS. This finding suggests that we may be able to target and regulate specific bacterial groups in the gut to prevent and treat AS.