Background/Purpose: Deep profiling of gut microbiota may reveal new pathways of how SpA and its related diseases such as Crohn’s disease (CD) and acute anterior uveitis (AAU) are initiated and perpetuated. The aim of our study was to characterize a shared gut microbiota signature for SpA and its related diseases, as well as for each individual disease, compared with individual controls.

Methods: Patients were recruited with a definite diagnosis of axial SpA, AAU or CD, and were compared with controls (patients with back pain and previously ruled out SpA/CD/AAU diagnosis). Fecal samples were collected, and microbiota composition was determined by 16S rRNA gene sequencing, followed by computational analysis using the LotuS pipeline (v1.62) and referencing the taxonomic classification by the SILVA (v138), Greengenes (v13.5) and HITdb (v1.0.0) databases. 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 with 63 control individuals. The average age was 39.1±12.3 years (mean±SD) and 53% were males. The prevalence of HLA-B27 was 63.0% by all patients (87.4% in axial SpA, 77.3% in AAU and 8.9% in CD patients) compared to 7.9% by control individuals.

At the phylum level, patients with axial SpA, AAU and CD were dominated by Firmicutes, followed by Bacteroidetes and Actinobacteria, except for CD patients who were richer in Proteobacteria than Actinobacteria. At the genus level, patients displayed a shared gut microbiome signature differing from that of control individuals including enrichments in Veillonella and Lactobacillus (that correlated with increased CRP) and a strong depletion of Blautia and other Firmicutes such as Fusicatenibacter, Lachnospiraceae FCS020 and Roseburia. 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 depleted in Cupriavidus. HLA-B27+ individuals were enriched in several Firmicutes, most notably Faecalibacterium, but also Rominococcaceae and Lachnospiraceae NK4A136. AAU patients shared many of the same enrichments, including a significant increase in Coprococcus.

Conclusion: There is a robust shared taxonomic signature among related immune-mediated diseases, in addition to individual disease phenotype signatures. Patients shared a strong depletion in Blautia and enrichment in Veillonella and Lactobacillus. SpA patients were uniquely enriched in Collinsella.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/axial-spondyloarthritis-and-its-related-immune-mediated-diseases-share-a-gut-microbiome-signature-besides-their-own-distinctive-profile/