Session Type: Abstract Submissions (ACR)
Background/Purpose The intestinal microbiota plays a central role in both health and disease. Beyond shaping local immune responses in the gut, it is increasingly clear that the microbiota also influencesimmune responses in the periphery. With respect to spondyloarthopathies (SpAs), the development of reactive arthritis following enteric infection and the resistance of germ-free animals to disease supports its contribution to pathogenesis. In this study we used the HLA-B27 transgenic rat model to test the hypothesis that expression of HLA-B27, a key SpA risk allele, shapes the intestinal microbiome and may contribute to B27-associated spondyloarthropathy.
Methods We used both 16s sequencing and quantitative real-time PCR to analyze the microbiota community structure of WT and B27+ rats. Samples were collected from ileum, cecum and colon of rats during the post-weaning period (3-6 wks), at disease onset (8-12 wks) and after the establishment of disease (15+ weeks). Samples were collected from multiple rat lines expressing the HLA-B27 transgene, including those on the Fischer, Lewis and DA backgrounds.
Results We identified a number of B27-dependent changes to the intestinal microbiome, including eight operational taxonomic units (OTUs) that were more abundant in the microbiota of B27 animals relative to controls on all three backgrounds examined. These included Bacteroides, Clostridia and Lactobacilli spp. Notably, segmented filamentous bacteria (SFB) were a dominant member of the ileal microbiota of disease-susceptible Lewis and Fischer rats but largely absent in disease-resistant DA rats. Mucus-degrading bacterium Akkermania muciniphila was upregulated ~300 fold in B27 vs WT animals in disease-susceptible rats on the Fischer background. Many of these changes were not evident during the post-weaning period.
Conclusion HLA-B27 expression strongly modulates the intestinal microbiota and B27-dependent changes were observed in all tissue sites examined. This provides compelling rationale to functionally examine the contribution of defined bacteria to B27-mediated SpA and to identify their association with disease in humans. The strong age-dependent effects on the microbiota indicate this is a critical consideration for such studies.
R. A. Colbert,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hla-b27-expression-shapes-the-intestinal-microbiota/