Abstract

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.

Highlights

  • Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease [1], affecting nearly 1% of the Caucasian population [2]

  • The early-onset RA (eRA) patients were dominated by women, and present or past smoking was more prevalent among eRA patients than controls

  • The mean number of observed amplicon sequence variants (ASVs) was significantly higher in the saliva microbiota of eRA than in healthy controls (p = 0.005 at a sequencing depth of 17,333 reads and p < 0.001 at a sequencing depth of 26,000 reads; Figure 1a)

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Summary

Introduction

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease [1], affecting nearly 1% of the Caucasian population [2]. The presence of autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs), are hallmarks of RA [3]. In parallel with the pre-symptomatic evolution of autoantibodies, RA markers have expanded to include circulating pro- and anti-inflammatory cytokines [4,5]. The oral cavity, which is the first part of the alimentary tract, harbors billions of bacteria with more than 700 different identified species [8], of which certain species may trigger RA autoimmunity [6,7,9,10]

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