# Joint Microbiota Suggests Articular Dysbiosis in Experimental Murine Spondyloarthritis and Histological Detection of Bacteria in Human SpA Joints

## TL;DR

This study shows that bacteria are present in the joints of mice with spondyloarthritis and humans, suggesting a possible role in disease progression and systemic spread.

## Contribution

The study identifies joint microbiota dysbiosis and bacterial translocation in experimental and human spondyloarthritis.

## Key findings

- Bacteria were more abundant in the joints of diseased mice compared to healthy ones.
- Shared bacterial species were found in the gut, joints, and systemic tissues like the liver and heart.
- Bacterial components colocalized with inflammatory markers in joint cells, supporting a role in inflammation.

## Abstract

Recent studies have provided evidence supporting the presence of a commensal joint microbiome; however, its role in the pathogenesis of spondyloarthritis (SpA) remains unclear. This study aimed to characterize the joint microbiome and assess its role in bacterial dissemination and systemic involvement.

DBA/1 mice with spontaneous arthritis (SpAD) and healthy BALB/c mice, as well as biopsies from SpA patients, were analyzed by histology (Gram staining and IHC), short-read next-generation sequencing of the 16S rRNA gene amplicons, and transcriptomics. Shared bacterial species were evaluated across tissues, including the liver and heart, and the colocalization of bacterial and inflammatory markers was assessed using double indirect immunofluorescence (IIF).

Bacteria were detected in the joints of healthy and SpAD mice, with significantly greater abundance in the latter. Microbiome analysis revealed distinct bacterial communities, with genera, such as Pelomonas and Aerococcus uniquely identified in the joints of SpAD mice, indicating a state of dysbiosis. Several bacterial species, including Prevotella sp., Ruminococcus gnavus, Lactobacillus johnsonii, and Limosilactobacillus reuteri, were detected in both the gut and joints of SpAD mice. Additionally, bacterial DNA from these taxa was also amplified from liver and heart tissues, indicating systemic dissemination. Transcriptomic analysis revealed dysregulated bacterial response pathways in SpAD joints, with an inflammatory profile distinct from that observed in gut tissues. Double IIF confirmed the colocalization of bacterial components with proinflammatory cytokines in joint cells. In human SpA biopsies, Gram staining and IHC also identified bacteria in sacroiliac and tarsal tissues.

These findings confirm the presence of bacteria in the joints of healthy and SpAD mice, as well as SpA patients. The joint microbiome differs between healthy and diseased mice, contributing to inflammation through dysregulated bacterial responses. Additionally, the identification of shared bacterial species between the gut and joints, as well as their detection in the liver and heart, supports the hypothesis of bacterial dissemination consistent with translocation and systemic involvement.