Causal Relationship Between Gut Microbiota and Ankylosing Spondylitis and Potential Mediating Role of Inflammatory Cytokines: A Mendelian Randomization Study

Associations between gut microbiota and ankylosing spondylitis have been discovered in previous studies, but whether these associations reflect a causal relationship remains inconclusive. Aiming to reveal the bidirectional causal associations between gut microbiota and ankylosing spondylitis, we utilized publicly available genome wide association study summary data for 211 gut microbiota (GM) taxa and ankylosing spondylitis (AS) to conduct two sample mendelian randomization analyses. Mediation analysis was performed to explore mediating inflammatory cytokines. We found that genetically predicted higher abundance of Lactobacillaceae family, Rikenellaceae family and Howardella genus had suggestive associations with decreased risk of ankylosing spondylitis while genetic proxied higher abundance of Actinobacteria class and Ruminococcaceae_NK4A214_group genus was associated with increased risk of ankylosing spondylitis. IL23 and IFN-γ were potential mediating cytokines for GM dysbiosis, especially for Actinobacteria class, leading to AS. Our study provided a new exploration direction for the treatment of AS. Lactobacillaceae family, Rikenellaceae family, Howardella genus, Actinobacteria class and Ruminococcaceae_NK4A214_group genus are expected to become new therapeutic targets and monitoring indicators for AS.