Abstract:Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis. Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. Thi… Show more
“…There is a strong correlation of contributions from oral pathogens in their development without specific understanding of the mechanisms leading to the disease pathogenesis. The focus of this review is on the periodontal keystone pathogen Porphyromonas gingivalis [1,2], and its secreted peptidyl arginine deiminase (PPAD) enzyme in the development of the extraoral autoimmune and inflammatory diseases mentioned above [3–7] (Figure 1). 10.1080/20002297.2018.1487742-F0001Figure 1.Schematic to show additive effect from an oral condition such as periodontitis to the development of mixed pathologies through smoking, atherosclerosis, and rheumatoid arthritis with direct inflammatory mediator input from P. gingivalis infection to Alzheimer’s disease.…”
Section: Introductionmentioning
confidence: 99%
“…Thus, P. gingivalis is a typical example of a pathogen that shows this trait by adapting to challenging inflammophilic environments of the host directed to kill it [8]. The virulence and potential pathogenic effects of P. gingivalis are diverse and, through them, this bacterium can affect many different organs and diseases [3,6,7,9,10]. The virulence factor under focus here is the enzyme P. gingivalis peptidyl-arginine deiminase (PPAD).…”
Section: Introductionmentioning
confidence: 99%
“…The sporadic form is common with potential for the role for susceptibility genes and pathogens as well as co-morbidities, similar to those implicated in the aforementioned human complex diseases [7]. Due to the rising number of dementia cases, and the paucity of adequate treatment for AD, there is a consensus for preventing the disease in at least a third of all sporadic AD cases by modifying behavioural life-styles [10].…”
Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer’s disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.
“…There is a strong correlation of contributions from oral pathogens in their development without specific understanding of the mechanisms leading to the disease pathogenesis. The focus of this review is on the periodontal keystone pathogen Porphyromonas gingivalis [1,2], and its secreted peptidyl arginine deiminase (PPAD) enzyme in the development of the extraoral autoimmune and inflammatory diseases mentioned above [3–7] (Figure 1). 10.1080/20002297.2018.1487742-F0001Figure 1.Schematic to show additive effect from an oral condition such as periodontitis to the development of mixed pathologies through smoking, atherosclerosis, and rheumatoid arthritis with direct inflammatory mediator input from P. gingivalis infection to Alzheimer’s disease.…”
Section: Introductionmentioning
confidence: 99%
“…Thus, P. gingivalis is a typical example of a pathogen that shows this trait by adapting to challenging inflammophilic environments of the host directed to kill it [8]. The virulence and potential pathogenic effects of P. gingivalis are diverse and, through them, this bacterium can affect many different organs and diseases [3,6,7,9,10]. The virulence factor under focus here is the enzyme P. gingivalis peptidyl-arginine deiminase (PPAD).…”
Section: Introductionmentioning
confidence: 99%
“…The sporadic form is common with potential for the role for susceptibility genes and pathogens as well as co-morbidities, similar to those implicated in the aforementioned human complex diseases [7]. Due to the rising number of dementia cases, and the paucity of adequate treatment for AD, there is a consensus for preventing the disease in at least a third of all sporadic AD cases by modifying behavioural life-styles [10].…”
Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer’s disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.
“…A variation of similar clinical characters may derive from mild‐to‐severe forms of the disease with different genetic backgrounds . In both diseases, of course, the risk factors deriving from the lifestyle play a large role, without forgetting the possibility that environment modifies the epigenomes or the host/pathogen interactome . To date, genome‐wide association (GWA) or large‐scale candidate gene studies have linked periodontitis significantly with variation in only four genes .…”
Clinical periodontitis is associated with an increased risk for cardiovascular diseases (CVDs) through systemic inflammation as the etiopathogenic link. Whether the oral microbiota, especially its quality, quantity, serology, and virulence factors, plays a role in atherogenesis is not clarified. Patients with periodontitis are exposed to bacteria and their products, which have access to the circulation directly through inflamed oral tissues and indirectly (via saliva) through the gastrointestinal tract, resulting in systemic inflammatory and immunologic responses. Periodontitis is associated with persistent endotoxemia, which has been identified as a notable cardiometabolic risk factor. The serology of bacterial biomarkers for oral dysbiosis is associated with an increased risk for subclinical atherosclerosis, prevalent and future coronary artery disease, and incident and recurrent stroke. In addition to species-specific antibodies, the immunologic response includes persistent, cross-reactive, proatherogenic antibodies against host-derived antigens. Periodontitis may affect lipoprotein metabolism at all levels, and all lipoprotein classes are affected. Periodontitis or its bacterial signatures may be involved not only in increased storage of proatherogenic lipids but also in attenuation of the anti-atherogenic processes, thereby putatively increasing the net risk of atherosclerosis. In this review we summarize possible molecular mediators between the dysbiotic oral microbiota and atherosclerotic processes.
“…Different types of cells/organisms in physical contact with one another communicate in various ways, including through protein:protein interactions, for example, enabled by a plethora of bacterial secretion systems, pili and vesicles, and including the injection of proteins by one organism into another, whose behaviour/metabolism then becomes modified by PPI between native and the injected foreign proteins, as is the case of many host:pathogen interactions that result in disease. The use of interactomics to map such heterologous protein interactions is yielding important new insights into the pathogen-caused re-wiring of host protein interactions that result in direct pathological changes in cellular/organismal metabolism (Sana et al, 2015;Schweppe et al, 2015;Nicod et al, 2017), and, in some instances, more insidious, less direct, noncommunicable diseases, like Alzheimer's, diabetes and cardiovascular disease (Carter et al, 2017).…”
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