Affinity between gut microbiota and ankylosing spondylitis: insight from causal analysis

Ankylosing spondylitis (AS) is a chronic inflammatory disease with a global prevalence, primarily affecting the axial skeleton. While traditional therapies are often employed before surgical interventions, pharmacotherapy is typically reserved for cases of unstable AS condition. The gut microbiota has been implicated in numerous pathological conditions. However, its specific role in AS remains poorly understood. To address this knowledge gap, we applied Mendelian randomization (MR) to explore potential causal relationships between gut microbiota and AS. For this analysis, we utilized two large-scale genome-wide association study datasets: one comprising 18 340 individuals across 24 cohorts for human gut microbiota, and another consisting of 9069 AS cases and 1550 controls for AS susceptibility. Following heterogeneity testing, assessment of horizontal pleiotropy and application of multiple MR methods and 'leave-one-out' analysis, we identified 10 bacterial traits associated with AS risk. These include four risk-increasing factors: Actinobacteria (class), Streptococcaceae (family), Enterorhabdus (genus), and the Ruminococcaceae NK4A214 group (genus); and six risk-decreasing factors: Lactobacillaceae (family), Rikenellaceae (family), Anaerotruncus (genus), Eubacterium oxidoreducens group (genus), Howardella (genus), and Oscillibacter (genus). This study provides novel insights into the gut-spine axis and suggests potential avenues for AS management through microbiota-targeted interventions.