Background/Purpose: Reactive arthritis (ReA) is an inflammatory condition occurring several weeks after gastrointestinal (GI) or genitourinary (GU) infections. HLA-B27 positivity is considered a risk factor, though not necessarily predictive of disease incidence. Among non-genetic factors, the intestinal microbiome may play a role in disease susceptibility. The objective of this study was to characterize the gut microbiota and host gene interactions in ReA.

Methods: Adult ReA (n=32) and control (n=32) subjects with preceding GI and/or GU infections that did not develop arthritis were prospectively recruited in Guatemala, a highly prevalent geographic region for this disease. Clinical variables, HLA status, and fecal samples were collected. Fecal DNA was extracted and high-throughput sequencing of the V4 hypervariable region of bacterial 16S rRNA was performed using the MiSeq Illumina platform (150 bp read length, paired-end protocol) to determine intestinal microbiota composition. Data was analyzed with Quantitative Insights into Microbial Ecology (QIIME), R, Linear discriminant analysis Effect Size (LEfSe), and co-occurrence networks.

Results: ReA subjects showed no significant differences from controls in gut bacterial alpha or beta diversity. Furthermore, there were no differences when subjects were grouped by prior exposure to antibiotics or sulfasalazine. However, there was a higher abundance of Erwinia and Pseudomonas, and increased prevalence of typical enteropathogens associated with ReA. In fact, at least one enteropathogen was present in 71.9% of ReA subjects vs 46.8% of controls (p<0.05). LEfSe analysis showed that subjects with ultrasound evidence of enthesitis were enriched in Campylobacter, while subjects with uveitis and radiographic sacroiliitis were respectively enriched in Erwinia and unclassified Ruminococcaceae, and both enriched in Dialister (log LDA >2). Host genetics, particularly HLA-A24, were associated with differences in gut microbiota diversity irrespective of disease status. We determined several co-occurring taxa that were also predictive of HLA-A24 status, including Ruminococcaceae-Rikenellaceae–Coriobacteriaceae and Prevotellaceae-unclassified Sphingobacteriales–Elusimicrobiaceae.

Conclusion: This is the first culture-independent study characterizing the gut microbial community of ReA. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota host-genetic relationships may further clarify the pathogenesis of ReA and related spondyloarthropathies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gut-microbiota-perturbations-in-reactive-arthritis/