Oral microbial dysbiosis linked to worsened periodontal condition in rheumatoid arthritis patients

Jôice Dias Corrêa,Gabriel R Fernandes,E Xiao,Mayra Laino Albiero,Dana T Graves,Gilda Aparecida Ferreira,Fernando Q Cunha,Antônio Lúcio Teixeira,Débora Cerqueira Calderaro,Janine Mayra Silva,Chiranjit Mukherjee,Eugene J Leys,Santuza Maria Souza Mendonça,Tarcília Aparecida Silva

doi:10.1038/s41598-019-44674-6

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. Individuals with RA have a higher risk of periodontitis and periodontitis has been linked to RA through the production of enzymes by periodontal pathogens that citrullinate proteins. This linkage is supported by findings that periodontitis is associated with increased RA severity and treatment of periodontitis can improve the symptoms of RA. The possible mechanism for this association is through dysbiosis of the oral microbiota triggered by RA-induced systemic inflammation. We examined the RA status of subjects by measuring the number of tender and swollen joints, anti-citrullinated protein antibody and rheumatoid factor. Periodontal disease status and salivary cytokine levels were measured, and dental plaque analyzed by 16S rRNA high throughput sequencing. RA patients had a higher bacterial load, a more diverse microbiota, an increase in bacterial species associated with periodontal disease, more clinical attachment loss, and increased production of inflammatory mediators including IL-17, IL-2, TNF, and IFN-γ. Furthermore, changes in the oral microbiota were linked to worse RA conditions. Our study provides new insights into the bi-directional relationship between periodontitis and RA and suggest that monitoring the periodontal health of RA patients is particularly important.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation
A relationship between RA and periodontitis has previously been reported, but the impact of RA on the subgingival microbiota linked to periodontal disease has not been thoroughly investigated and mechanisms for the potential impact have not been addressed[20,21,22,23,24,25]
IL-2, IFN-γ, TNF and IL-33 exhibited an approximately two-fold increase in RA subjects without periodontitis compared to matched controls

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. Microbial populations co-exist in equilibrium with the host The change in this equilibrium is linked to the pathogenesis of oral diseases such as periodontitis[1,2]. It has been proposed that periodontal disease and RA are linked by periodontal pathogens that produce enzymes capable of modifying proteins to enhance their antigenicity through the addition of malondialdehyde-acetaldehyde, citrullination and carbamylation[8,10,11]. These anti-cyclic citrullinated peptide (CCP) antibodies can be detected before RA onset and have been identified as an etiologic factor in the disease process[12]. Subjects Females % Age, years Current Smokers RA duration, years Disease active parameters Tender joints Swollen joints DAS28 Autoantibody status ACPA positive, % Medications Methotrexate Prednisone Biological agent Periodontal parameters PD (mm) CAL (mm) BOP (% sites) Missing teeth Plaque Index Tooth brushing (times/day)

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Conclusion