Dysbiotic Subgingival Microbial Communities in Periodontally Healthy Patients With Rheumatoid Arthritis

Abstract

Objective Studies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. This study was undertaken to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with RA to those without RA.

Methods Subgingival plaque was collected from periodontally healthy individuals (22 with RA and 19 without RA), and the 16S gene was sequenced on an Illumina MiSeq platform. Bacterial biodiversity and co‐occurrence patterns were examined using the QIIME and PhyloToAST pipelines.

Results The subgingival microbiomes differed significantly between patients with RA and controls based on both community membership and the abundance of lineages, with 41.9% of the community differing in abundance and 19% in membership. In contrast to the sparse and predominantly congeneric co‐occurrence networks seen in controls, RA patients revealed a highly connected grid containing a large intergeneric hub anchored by known periodontal pathogens. Predictive metagenomic analysis (PICRUSt) demonstrated that arachidonic acid and ester lipid metabolism pathways might partly explain the robustness of this clustering. As expected from a periodontally healthy cohort, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were not significantly different between groups; however, Cryptobacterium curtum, another organism capable of producing large amounts of citrulline, emerged as a robust discriminant of the microbiome in individuals with RA. Conclusion Our data demonstrate that the oral microbiome in RA is enriched for inflammophilic and citrulline‐producing organisms, which may play a role in the production of autoantigenic citrullinated peptides in RA.

Rheumatoid arthritis (RA) has been associated with periodontal disease, a bacterially initiated chronic inflammation that leads to the destruction of tooth‐supporting tissue 1. Although periodontal disease and RA share similar inflammatory pathways as well as genetic and environmental risk factors, these are insufficient to explain this connection 1.

While the cause of RA remains unknown, it has been hypothesized that oral microbiota 2, 3, in particular the periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, may play a critical role in its pathogenesis 4, 5.

Studies using next‐generation sequencing methods have demonstrated that the oral microbiome is altered in RA 6, 7. However, the majority of those studies included individuals with moderate to severe periodontitis 7 or individuals whose periodontal health status was not established 6. Periodontitis by itself is a significant modifier of the oral microbiome 8, making it difficult to dissect the relative contributions of periodontitis and RA to microbial dysbiosis.

Given the potential role oral bacteria may play in the pathogenesis of RA, we set out to characterize the periodontal microbiome in periodontally healthy individuals with and those without RA, using next‐generation sequencing.