Porphyromonas gingivalis

Extensive study has been conducted around the world identifying periodontitis-causing oral pathogens, primarily Porphyromonas gingivalis, as having a strong association with the etiopathogenesis of rheumatoid arthritis (RA). This organism has been shown to translocate from infected gums to distant sites in the body and has been found in the joints, as well as having unique enzymatic properties that lead to the creation of auto-reactive antibodies that lead to the breaking of self-tolerance, called anti-cyclic citrullinated peptides (anti-CCP). Anti-CCP is an auto-antibody used in the diagnosis of RA and has been determined to be involved in the initiation of RA and is viewed as being a harbinger of disease severity in genetically-predisposed individuals.

The aggravation of arthritis by periodontitis is dependent of IL-17 receptor A activation. J Clin Periodontol. 2017 May 12.

Brazilian researchers conclude that the infection, Porphyromonas gingivalis, a known infectious cause of gum disease, resulted in greater joint damage in infected, as opposed to non-infected, mice and that this correlated to higher tumor necrosis factor (TNF) and interlukin-17 (IL-17) production, leading to greater neutrophilic infiltration of the joints.

Cross-Sectional Evaluation of Periodontal Status and Microbiologic and Rheumatoid Parameters in a Large Cohort of Patients With Rheumatoid Arthritis. J Periodontol. 2017 Apr;88(4):368-379.

German researchers studied the periodontal conditions and microbiologic findings of 168 rheumatoid arthritis (RA) patients to determine its impact on rheumatic disease severity against a healthy control group. Decayed, missed and filled teeth were significantly higher in the RA group, as well as a greater incidence of moderate to severe periodontitis, especially in rheumatoid factor (RF)-positive patients. The gum infection, Trepenoma denticola, was prevalent in the older RA patients, and correlated with worse periodontal status. Patients who were seropositive for anti-cyclic citrullinated peptide (anti-CCP) antibodies were also found in higher concentrations in the presence of other infections, causative of gum disease, Porphyromonas gingivalis and Fusobacterium nucleatum. Although the researchers are unclear about the relationship of periodontitis with RA, they conclude that RA patients had worse periodontal conditions than healthy controls.

Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population. BMJ Open. 2017 Jan 31;7(1):e011916.

Finnish researchers sought to determine the relationship between rheumatoid arthritis (RA) and periodontitis, with a focus on anti-rheumatic disease-modifying drugs (DMARDs) and whether or not these drugs played any role in periodontal health. Although no relationship was evident with regard to the use of DMARDs and an association with periodontal disease, patients with both early RA (and no DMARDs) and chronic RA (unresponsive to DMARDs) were found to have poorer periodontal health than healthy controls.

Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis – a systematic review and meta-analysis. Clin Oral Investig. 2017 Jan;21(1):33-42.

Swiss researchers conducted a systematic review and meta-analysis to determine if antibody titers to Porphyromonas gingivalis (P. gingivalis), a causative infection of periodontal disease, were higher in rheumatoid arthritis (RA) patients as opposed to healthy controls, with and without gum disease. The authors based their analysis upon the fact that P. gingivalis has been shown to citrullinate peptides and proteins, suggestive of this infection playing a role in both periodontal disease and RA. They concluded that to date the research seems to indicate that RA patients had a significantly higher incidence of antibody titers to P. gingivalis than healthy controls and that this bears clinical relevance in terms of alerting rheumatologists to the need for antibody screening in order to encourage improved periodontal health in RA patients.

Does the buck stop with the bugs?: an overview of microbial dysbiosis in rheumatoid arthritis. Int J Rheum Dis. 2016 Jan;19(1):8-20.

Researchers in India propose a comprehensive whole body mechanistic approach to the pathogenesis of rheumatoid arthritis (RA), which they assert is the result of a combination of host genetics, dietary factors, environmental cues, infections that originate in the lungs, mouth, gut and genitourinary tract, as well as direct DNA evidence for infection translocation to the joints.  Infections, such as Porphyromonas gingivalis (P. gingivalis) and the production of  cross-reactive anti-cyclic citrullinated peptides (anti-CCP) is discussed, in addition to microbial alterations in the human gut microbiome and the effects of these on host immune response. The authors detail the antimicrobial effects of commonly used DMARDs, such as sulphasalazine and hydroxychloroquinine, as well as tetracycline antibiotics, macrolides, levofloxacin, dapsone, ceftriaxone and metronidazole, acknowledging their antimicrobial immune-modulatory effects. A prevention and treatment approach is outlined, employing antimicrobials, in addition to dietary modifications, probiotics, and DMARDs to modulate RA pathogenesis is described, in acknowledgment that gaps in understanding RA continue to be challenging.

Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis. Arthritis Res Ther. 2016 Oct 26;18(1):249.

American and Norwegian researchers collaborated in a study of HLA DR1 mice, genetically predisposed to rheumatoid arthritis (RA), infected with Prophyromonas gingivalis, an infectious cause of periodontal disease. Infected mice were found to have a significant increase in Th17 cells in peripheral blood and cervical lymph nodes, a sudden increase in systemic cytokine activity, femoral bone density loss, and became seropositive for anti-cyclic citrullinated peptide (anti-CCP) auto-reactive antibodies. The authors conclude that based on the generation of anti-CCP autoantibodies in response to P. gingivalis, demonstrates a role for a shared etiope between the periodontitis and RA and provides evidence for this infection as an autoimmune trigger.

Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther. 2016 Sep 7;18:201.

In a collaborative study, between Swedish, Polish, and American researchers, to determine if rheumatoid arthritis (RA) onset is preceded by the production of Porphyromonas gingivalis (P. gingivalis) antibodies and anti-citrullinated protein antibodies (ACPA), an autoantibody marker for RA. Two-hundred and fifty-one patients with RA who had donated blood approximately 5 or 6 years prior to symptom onset, were compared with the blood samples of 198 individuals without RA. Findings revealed that antibodies to P. gingivalis were significantly elevated in the RA group, in the years prior to disease onset, and that ACNP concentrations increased in some pre-symptomatic individuals over time.

Periodontal bacterial colonization in synovial tissues exacerbates collagen-induced arthritis in B10.RIII mice. Arthritis Res Ther. 2016 Jul 12;18(1):161.

In a study using a collagen-induced arthritis (CIA) murine model, researchers sought to determine a link between oral microbes and rheumatoid arthritis (RA). CIA mice were infected with an oral bacterial mixture of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia and monitored for 24 weeks before CIA induction to determine the ability of these organisms to colonize the gums and tooth sockets, as well as any systemic response. Conclusions drawn were that intravascular dissemination to the joints leading to arthritis and its exacerbation, specifically by P. gingivalis, lends itself to the theory that the autoimmune process in the CIA mouse model can be triggered by this infection and that this bacteria has the ability to translocate to colonize distant sites, like the joints.

Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross-Sectional Study. J Periodontol. 2016 Apr;87(4):346-56.

In a Columbian study of both 119 individuals with pre-rheumatoid arthritis (pre-RA), having a risk for developing the disease, and 48 early-rheumatoid arthritis (e-RA) patients with recent onset disease symptoms, it was found that those with pre-RA had significant inflammatory periodontal gum disease. Infection reactivity (IgG) to Porphyromonas gingivalis, a causative infection of  gum disease, and elevations in anti-citrullinated protein antibodies (ACPA) was found to be significant in pre-RA patients, as well as the findings of an association in disease activity markers for those with eRA.

The association between rheumatoid arthritis and periodontitis. Best Pract Res Clin Rheumatol. 2015 Apr;29(2):189-201.

Australian researchers examine the relationship between periodontitis and rheumatoid arthritis (RA), stating that, “Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis.” They specify the role of the infection, Porphrymonas gingivalis, and its “unique enzymatic properties” that result in the production of anti-cyclic citrullinated peptide (anti-CCP) immune responses. These authors assert that these findings should help to provide an area of focus for treatment, prevention and risk assessment in RA.

Predominant immunoreactivity of Porphyromonas gingivalis heat shock protein in autoimmune diseases. J Periodontal Res. 2012 Dec;47(6):811-6.

South Korean researchers published significant findings of seroreactivity to a particular peptide (Pep19) of the chronic periodontal infection, Porphyromonas gingivalis (Heat Shock Protein 60 or HSP60) and its correlation to autoimmune diseases such as, diabetes mellitus, and rheumatoid arthritis, as well as atherosclerosis. The authors state that these disease states appear to be, “triggered and aggravated by the pathogen-driven antigenic peptide from Porphyromonas gingivalis HSP60.”

Periodontal Disease as a Risk Factor for Rheumatoid Arthritis: A Systematic Review. JBI Libr Syst Rev. 2012;10(42 Suppl):1-12.

Australian researchers conducted a systematic review of periodontal disease and its causative microbial infections as a risk factor for rheumatoid arthritis (RA), and the finding of distinct similarities in the clinical and pathogenic mechanisms of bone and soft tissue destruction in both diseases. Both are also subject to the production of inflammatory cytokines such as interleukin-1, tumor necrosis factor and prostaglandin E2. The authors point to a number of studies suggesting a relationship between periodontitis and rheumatoid arthritis and that one may have significant impact on the other.

The association between rheumatoid arthritis and periodontal disease. Arthritis Res Ther. 2010;12(5):218.

German researchers discuss the strong supporting scientific evidence for oral bacterial infections, the inflammation and resulting bone destruction that appears to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). The authors specifically point to the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination and seropositivity of rheumatoid factor (RF) and the anti-cyclic citrullinated peptide antibody (anti-CCP) in RA.

Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. 2010 Jan;233(1):34-54.

Researchers at The Kennedy Institute of Rheumatology of Imperial College London, in England, discuss the genetic, environmental, and autoimmune triad of rheumatoid arthritis (RA), as well as the strong, supportive evidence for Porphyromonas gingivalis as an etiologic agent of RA, which they state requires further investigation.

Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated rheumatoid arthritis. Med Hypotheses. 2009 Jun;72(6):732-5.

Chinese researchers postulate that Porphyromonous gingivalis (P. gingivalis) plays a critical role in the pathogenesis of periodontitis-associated rheumatoid arthritis (RA). P. gingivalis, colonizing the mouth and producing peptidylarginine deiminase (PAD) antigens, leads to the citrullination of RA autoantigen, such as fibrin, in the synovial tissues of the joint. When antigen-presenting cells (APC) are introduced to PAD in association with major histocompatibility complex (MHC) molecules, this leads to the production of anti-cyclic citrullinated peptide antibodies (anti-CCP). Bound by inflammatory cells, anti-CCP forms immune complexes, which leads to a complex cascade of complement activation. This process in turn drives inflammation that leads to RA onset and joint destruction and, hence, the loss of self-tolerance.

Rheumatoid arthritis is linked to oral bacteria: etiological association. Mod Rheumatol. 2009;19(5):453-6. doi: 10.1007/s10165-009-0194-9. Epub 2009 June 24.

A prolific researcher of infectious causes for rheumatoid arthritis (RA) and its treatment with antibiotic therapy, at the Division of Rheumatology of Nazilli State Hospital, in Nazilli, Turkey, reviewed the evidence of periodontitis and the role of causative organisms that are directly associated with the etiopathogenesis of RA. Additionally, this researcher states that findings of anerobic bacteria, such as, Porphyromonas gingivalis, Tannerella forsythensis, and Prevotella intermedia that have been identified in RA synovial fluid can be treated with antibiotics, such as ornidazole, levofloxacin, and clarithromycin that have been shown to be effective in RA.


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