Objective: Ankylosing spondylitis (AS) is a common, highly heritable immune‐mediated arthropathy that occurs in genetically susceptible individuals exposed to an unknown but likely ubiquitous environmental trigger. There is a close relationship between the gut and spondyloarthritis, as exemplified in patients with reactive arthritis, in whom a typically self‐limiting arthropathy follows either a gastrointestinal or urogenital infection. Microbial involvement in AS has been suggested; however, no definitive link has been established. The aim of this study was to determine whether the gut in patients with AS carries a distinct microbial signature compared with that in the gut of healthy control subjects.Methods: Microbial profiles for terminal ileum biopsy specimens obtained from patients with recent‐onset tumor necrosis factor antagonist–naive AS and from healthy control subjects were generated using culture‐independent 16S ribosomal RNA gene sequencing and analysis techniques.Results: Our results showed that the terminal ileum microbial communities in patients with AS differ significantly (P < 0.001) from those in healthy control subjects, driven by a higher abundance of 5 families of bacteria (Lachnospiraceae [P = 0.001], Ruminococcaceae [P = 0.012], Rikenellaceae [P = 0.004], Porphyromonadaceae [P = 0.001], and Bacteroidaceae [P = 0.001]) and a decrease in the abundance of 2 families of bacteria (Veillonellaceae [P = 0.01] and Prevotellaceae [P = 0.004]).Conclusion: We show evidence for a discrete microbial signature in the terminal ileum of patients with AS compared with healthy control subjects. The microbial composition was demonstrated to correlate with disease status, and greater differences were observed between disease groups than within disease groups. These results are consistent with the hypothesis that genes associated with AS act, at least in part, through effects on the gut microbiome.

Objective: Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin‐23 (IL‐23) signaling in AS pathogenesis.Methods: The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL‐23 receptor (IL‐23R) expression in T cells was determined in each subject group, and expression levels were compared.Results: The proportion of IL‐23R–expressing T cells in the periphery was 2‐fold higher in AS patients than in healthy controls, specifically driven by a 3‐fold increase in IL‐23R–positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL‐17 were unchanged. This increased IL‐23R expression on γ/δ T cells was also associated with enhanced IL‐17 secretion, with no observable IL‐17 production from IL‐23R–negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL‐17 production in response to stimulation with IL‐23 and/or anti‐CD3/CD28.Conclusion: Recently, mouse models have shown IL‐17–secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL‐23 is a maturation and growth factor for IL‐17–producing cells, increased IL‐23R expression may regulate the function of this putative pathogenic γ/δ T cell population.