OP0031 SHARED AND DISTINCT GUT MICROBIOME SIGNATURES IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS AND ITS RELATED IMMUNE-MEDIATED DISEASES
Authors: V. Rios Rodriguez, M. Essex, J. Rademacher, F. Proft, U. Löber, L. Marko, U. Pleyer, B. Siegmund, D. Poddubnyy, S. Forslund
Journal: Annals of the Rheumatic Diseases (2021)

Background: Immune-mediated diseases such as spondyloarthritis (SpA) consistently coincide with dysbiosis of the gut microbiota and frequently present with additional inflammatory pathologies such as Crohn’s disease (CD) and acute anterior uveitis (AAU). Deep profiling of gut microbiota may reveal new pathways of how SpA and its related diseases are initiated and perpetuated. Objectives: To identify the presence of shared and specific gut microbiota signatures for SpA and its related diseases as a whole, as well as for the individual diseases, relative to healthy controls. Methods: Patients were recruited with a definite diagnosis of axial SpA, AAU or CD and were compared to controls (patients with back pain and previously ruled out SpA/CD/AAU diagnosis). All patients were naïve to or did not receive treatment with biological disease-modifying antirheumatic drugs for at least 3 months before enrollment of the study. Fecal samples were collected and microbiota composition was determined by 16S rRNA gene sequencing, followed by computational analysis referencing the SILVA138 database. Nonparametric Wilcoxon tests were used to calculate differential abundances between binary groups, and the Spearman correlation was used with continuous covariates. Nested linear models and likelihood ratio tests were used to assess confounding with respect to patient characteristics, HLA-B27 expression, inflammatory markers, and the presence of other immune-mediated diseases. Results: A total of 300 patients were recruited for the study: 111 axial SpA, 110 AAU, and 79 CD patients and were compared to 63 control individuals. Fifty-three of patients were males with an age (mean±SD) of 39.1±12.3 years. The prevalence of HLA-B27 was 63.0% by patients compared to 7.9% by control individuals. A multivariate PERMANOVA test between the groups was significant (p&lt;0.001), revealing a difference in overall composition between the groups. At the phylum level, patients with axial SpA, AAU and CD contained higher abundances of Proteobacteria, Bacteroidetes and Fusobacteria, and lower abundances of Firmicutes and Actinobacteria compared to the control group. At the genus level, patients (with axial SpA, AAU and CD) displayed a shared gut microbiome signature differing from that of control individuals. Patients samples were strongly depleted in Blautia compared to the control group. Many of the differentially abundant taxa also correlated with increased inflammation as measured by C-reactive protein (CRP), including a depletion of Fusicatenibacter , Lachnospiraceae FCS020 and Roseburia , as well as an enrichment of Lactobacillus and Veillonella . By looking at each separate disease phenotype, CD patients differed significantly from the control individuals with respect to many genera. These primarily consisted of depletions in Clostridiales ( Roseburia , Coprococcus , Ruminococcaceae ), and enrichments of pathogen-harboring genera such as Escherichia-Shigella and Fusobacterium . Axial SpA patients were uniquely enriched in Collinsella and Holdemanella and depleted in Cupriavidus ; the enrichment of Lactobacillus and depletion of Blautia observed in all patient groups was also associated to the presence of axial SpA, though confounded by CRP. There were strong taxa associations to the presence of HLA-B27, including enrichment of Asteroleplasma , Coprococcus , Faecalibacterium , Rominococcaceae, Lachnospiraceae NK4A136 and Rikenellaceae . Conclusion: There is a robust shared taxonomic signature among related immune-mediated diseases, in addition to individual disease phenotype signatures. Patients frequently exhibited a strong depletion in Blautia and an enrichment in Lactobacillus as well as pathogen-harboring genera such as Escherichia-Shigella and Fusobacterium . Figure 1. Taxa associations within and between the groups resulting from comparing each with the control group and accounting for disease concomitance and patient characteristics (FDR ≤ 0.05). AAU, anterior acute uveitis; CD, Crohn’s disease; SpA, spondyloarthritis. Disclosure of Interests: None declared