Current evidence strongly supports an association between periodontitis and rheumatoid arthritis (RA) in a subset of susceptible individuals. The relationship between these conditions is underpinned by a complex interplay between chronic inflammation and subgingival bacterial infection. Several hypotheses have been proposed to explain the mechanistic basis of this association. Among these, the "two-hit" model is particularly compelling, as it suggests that inflammation, infection, or a combination of both may contribute to the initiation and progression of RA in predisposed individuals. According to this model, the progression of gingivitis and periodontitis, together with associated microbial dysbiosis, may promote protein citrullination, carbamylation, and the formation of malondialdehyde-acetaldehyde (MAA) adducts. These post-translational modifications may subsequently induce the production of autoantibodies before the clinical onset of joint inflammation and RA. Once synovial inflammation develops, additional citrullination, carbamylation, and MAA adduct formation may occur within the joint microenvironment, further amplifying autoantibody production. In previously sensitized individuals, such as those with chronic gingivitis or periodontitis, this secondary immune response may be substantially enhanced, resulting in increased joint inflammation and tissue destruction. Subgingival bacteria may also contribute directly, or indirectly, to the periodontitis/RA axis through translocation to distant tissues, induction of protein citrullination and other protein post-translational modifications, stimulation of autoantibody production, and exacerbation of inflammatory responses. Central to the role bacteria play in the periodontitis/RA axis is the emergence of functional alterations in the microbiome. Dysbiosis in the subgingival microenvironment, and the emergence and proliferation of recognized periodontal pathobionts, underpins these key elements. This, along with bacterial-induced inflammation and direct influence on immune player trafficking, results in a complex synergy within the mechanistic processes involved in the relationship between periodontitis and RA. In this narrative review, we critically examine the inflammatory and microbial mechanisms implicated in the interaction between periodontitis and RA and propose an updated framework integrating inflammation, dysbiosis, and autoimmunity.
Bartold et al. (Fri,) studied this question.