Background:Several studies have suggested a link between the two chronic inflammatory diseases, rheumatoid arthritis (RA) and periodontitis (PD) [1]. The diseases share similar environmental and genetic risks factors,e.g.,smoking [2] and the HLA-DRB1 alleles [3]. Several serum markers used in the diagnosis of RA have also been found to be elevated in PD,e.g.,anti-citrullinated proteins antibodies (ACPA) and rheumatoid factor (RF) [4]. The connection between PD and RA has been suggested to be explained by several periodontal pathogens,e.g., Aggregatibacter actinomycetemcomitansandPorphyromonas gingivalis, which have been suggested to induce the production of autoantibodies [5, 6].Objectives:To investigate the composition of the concerted saliva microbiota and its role in the development of RA, with the aim of improving the diagnostic tools.Methods:16S ribosomal RNA gene sequencing of saliva bacterial DNA isolated from a total of 61 early RA (eRA) patients and 59 healthy controls was made. The eRA (symptoms ≤ 12 months) was diagnosed at an Early Arthritis Clinic (fulfilling the 1987 ARA criteria) and matched with the controls for sex and age, except for two of the elderly cases. None of the individuals included in the study had taken antibiotics during the preceding 3 months. No one of the cases were treated with anti-rheumatic drugs except for corticosteroids in 16 cases the latest month.Results:All participants were classified into three hierarchical cluster groups based on their saliva microbiota and the distribution of eRA cases versus controls differed distinctly between the cluster groups. The microbiota from the eRA had higher species richness, differed in beta-diversity, and was enriched for species in the Fusobacterium and Porphyromonas genera, and for the Alloprevotella tannerae, Campylobacter gracilis, Capnocytophaga leadbetteri, Filifactor alocis, Fusobacterium nucleatum subsp. polymorphum, Neisseria elongate, Porphyromionas endodontalis and Prevotella pleuritidis species compared to controls. Combining two topped ranked species,A. tanneraeandCatonella morbisignificantly predicted eRA with an AUC score of 0.86 and a specificity and sensitivity of 0.80 and 0.85, respectively.The predicted functions of the microbiota in eRA patients were dominated by fatty acid metabolism, ornithine metabolism, glucosylceramidase, sphingolipids, beta-lactamase resistance, biphenyl degradation and 17-beta-estradiol 17-dehydrogenase metabolism.Conclusion:In this study a difference in oral microbiota diversity between eRA patients and healthy controls could be shown. Some of the eRA-associated oral bacteria have previously been suggested to play an aetiological role in the development of RA, but others have not been recognized earlier, such as A. tannerae, F. alocis, F. nucleatum subsp. polymorphum, and P. endodontalis, and may therefore be useful in RA risk assessment.References:[1]Fuggle, N.R., et al.,Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis.Front Immunol, 2016. 7: p. 80.[2]Heliovaara, M., et al.,Smoking and risk of rheumatoid arthritis.J Rheumatol, 1993. 20(11): p. 1830-5.[3]Katz, J., et al.,Human leukocyte antigen (HLA) DR4. Positive association with rapidly progressing periodontitis.J Periodontol, 1987. 58(9): p. 607-10.[4]Mikuls, T.R., et al.,Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.Arthritis Rheumatol, 2014. 66(5): p. 1090-100.[5]Konig, M.F., et al.,Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis.Sci Transl Med, 2016. 8(369): p. 369ra176.[6]Rosenstein, E.D., et al.,Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis.Inflammation, 2004. 28(6): p. 311-8.Disclosure of Interests:None declared
Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans