Both disease activity and HLA-B27 determine gut microbiome dysbiosis in spondyloarthritis

Objective: Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) and could critically be involved in the pathogenesis of this disorder. The objective of this study was to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity, in light of the putative influence of genetic background. Methods: Shotgun sequencing was performed on fecal DNA isolated from stool samples of two groups of adult volunteers: SpA (N = 102) and healthy controls (N = 63). A subset of healthy controls comprised aged-matched siblings of patients with known HLA-B27 status. Changes in gut microbiota composition were assessed based on species diversity, enterotypes, taxonomical and functional differences. Results: Dysbiosis was confirmed in SpA compared to healthy controls. Restriction of microbiota diversity was detected in patients with the most active disease and the abundance of several bacterial species was correlated to the Bath Ankylosing Spondylitis Disease Activity Index. Among healthy controls, significant differences in microbiota composition were also detected between HLA-B27 positive and HLA-B27 negative siblings. We highlighted a decreased abundance of several species in SpA patients, especially belonging to Clostridiales order. Among the few species of increased abundance Ruminococcus. gnavus was one of the top differentiating species. Conclusion: These findings reveal that genetic background, as well as the disease activity level, are likely to influence gut microbiota composition. It could be relevant for further research on chronic arthritis to focus on these key parameters.