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Objectives  Periodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host´s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA.    Methods  Salivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA.    Results  Differential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC &amp;gt;20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included  Alloprevotella  sp.,  Prevotella  sp.,  Haemophilus  sp., and  Actinomyces  sp. whereas  Granulicatella  sp.,  Veillonella  sp.,  Megasphaera  sp., and  Fusobacterium nucleatum  were the most highly enriched ASVs (log2 FC &amp;gt;20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included  Vampirovibrio  sp. having a positive correlation with non-RA group, and seven ASVs belonging to  Sphingomonas insulae ,  Sphingobium  sp.,  Novosphingobium aromaticivorans ,  Delftia acidovorans ,  Aquabacterium  spp. and  Sphingomonas echinoides  with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-α2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs  Sphingobium  sp.,  Acidovorax delafieldii ,  Novosphingobium  sp., and  Aquabacterium  sp.    Conclusion  Our results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.

Salivary Microbiota and Host-Inflammatory Responses in Periodontitis Affected Individuals With and Without Rheumatoid Arthritis