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Poten&al Role of Periodontopathogens in Rheumatoid Arthri&s   
 

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Potential Role of Periodontopathogens in Rheumatoid 
Arthritis 
Shaymaa Abdulkareem Nori, Batool Hassan Al-Ghurabi 

College of Dentistry, University of Baghdad, Iraq 

Abstract 

Periodontal disease, par/cularly the chronic form of periodon//s, is a widespread inflammatory 
condi/on caused by pathogenic bacteria, such as Porphyromonas gingivalis. This review explores the 
poten/al role of periodontopathogens, par/cularly Porphyromonas gingivalis, in the development and 
progression of rheumatoid arthri/s. Rheumatoid arthri/s is a systemic autoimmune disorder 
characterized by joint inflamma/on and damage. Both periodon//s and rheumatoid arthri/s share 
common inflammatory mechanisms, driven by proinflammatory cytokines and immune dysregula/on. 
Porphyromonas gingivalis, via its pathogenic determinants, that is, gingipains and pep/dyl arginine 
deiminase, facilitates the citrullina/on of proteins, leading to the genera/on of an/-citrullinated protein 
an/bodies, a key feature in rheumatoid arthri/s pathogenesis. The reciprocal rela/onship between 
periodon//s and rheumatoid arthri/s is further supported through evidence showing that individuals 
with periodon//s are at a higher risk for rheumatoid arthri/s, and vice versa. Both circumstances exhibit 
similar inflammatory pathways, involving cytokines like tumor necrosis factor alpha, interleukin 1 and 
interleukin 6 and /ssue degrada/on mediated by matrix metalloproteinases.  

Keywords: Rheumatoid arthri=s, 
Periodon==s, Porphyromonas gingivalis 

Cita9on: Nori SA, et al. Poten9al Role of 
periodontopathogens in Rheumatoid Arthri9s. Den9stry 
3000.1:a001 doi:10/5195/d3000.2025.808 
Received: December 25, 2024 
Accepted: January 5, 2025 
Published: February 14, 2025 
Copyright: ©2025 Nori SA, et al. This is an open access 
ar9cle licensed under a Crea9ve Commons ASribu9on 
Work 4.0 United States License. 
Email: batoolamms@codental.uobaghdad.edu.iq 

 

 

Introduction 

      Periodontal disease, 
encompassing gingivitis and 
periodontitis (PD), is defined by 
the inflammation of the gums and 
other structures, frequently 
resulting from the buildup of 
detrimental bacteria in the oral 
cavity. Specific 
periodontopathogens, particularly 
Porphyromonas gingivalis (P. 
gingivalis), have been associated 
with the onset and aggravation of 
systemic inflammation [1].   
Rheumatoid arthritis (RA) is a 
tenacious, systemic inflammatory 
condition that principally impacts 
the joints, culminating in pain, 

rigidity, and possible joint 
abnormalities. Precise RA etiology 
is unclear; nonetheless, it is 
recognized to engage a confluence 
of genetic, environmental, and 
immune-mediated variables [2].  
Research indicates that 
periodontopathogens may have a 
role in RA by generating 
autoantibodies, such as anti-
citrullinated protein antibodies 
(ACPA), which activate immune 
responses that exacerbate joint 
inflammation. The bidirectional 
link between periodontal disease 
and RA, where in one condition 
may affect the onset or 
advancement of the other, has 
generated significant scholarly 

interest [3,4].  
This review aims to examine the 
potential link between periodontal 
infections and RA, focusing on 
how periodontopathogens, 
especially P. gingivalis, may 
contribute to the initiation of 
immune responses that facilitate 
the onset and advancement of RA.  

Materials and Methods 

       For this review, the authors 
executed an electronic search 
across many pertinent scientific 
databases, including SCOPUS, 
Google Scholar, PubMed, MDPI, 
and ResearchGate. The 
preliminary evaluation 
encompassed 130 publications 



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published from 2020 to 2024 that 
featured the keywords 
“periodontitis,” “Rheumatoid 
arthritis,” and “Porphyromonas 
gingivalis.”  

Inclusion criteria  

       This study included recent 
papers, reviews, and case-control 

studies; all articles included in this 
review were published in English.  

Exclusion criteria  

       Articles and research 
published prior to 2020 were 
omitted, as illustrated in Figure 1. 

 

Figure 1. Progression of the search and 
selection procedure. 

Periodontitis 

       Periodontitis is a persistent, 
damaging, and permanent 
inflammatory condition. It is the 
predominant cause of osteopenia 
and an infectious inflammatory 
ailment affecting humanity [5]. 
The World Health Organization 
classifies PD as unprecedented 
global event, exhibiting concerning 
frequency among various age 
demographics and geographic 
areas. It impact around 19% of the 
world's residents, representing 
more than a billion instances. The 
data concerning European nations 
reveals that over 50% of the 
population may experience some 
variant of PD, with over 10% 
afflicted by its severe 
manifestation. Incidence increases 
up to 70–85% among individuals 
of 60–65 years old [6]. From 1990 
to 2019, PD prevalence rate rose 
globally by 8.44% [7,8]. The 
worldwide load of PD is 
considerable and has markedly 
escalated throughout the last 
three decades, posing a huge 

public health concern and 
necessitating the pursuit of novel 
therapeutic interventions [6].  

Pathogenesis of Periodontitis 

       The pathogenesis of 
periodontal disease is defined by 
the interplay between bacterial 
plaque accumulation and 
inflammatory responses in the 
gingiva [9]. This connection 
activates fundamental molecular 
routes which ultimately result in 
the activation of host-derived 
proteases. This leads to 
periodontal ligaments marginal 
fibers degradation, junctional 
epithelium displacement, and 
subsequent bacterial biofilm 
proliferation along the root 
surface apically [10,11]. The 
microbiology of PD is intricate, 
primarily characterized by a 
transition in the microbial 
population from a largely Gram-
positive, aerobic, health-
associated biofilm to a 
predominance of Gram-negative 
anaerobes. Fundamental 

molecular investigations have 
found complexes of various 
bacterial species linked to severe 
chronic periodontitis, specifically 
P. gingivalis, Tanerella forsythia, 
and Treponema denticola [12]. A 
recent study shown that microbial 
populations associated with 
various periodontal conditions 
altered in an asynchronous 
manner during the reconstruction 
of biofilms following its initial 
elimination using supragingival 
cleaning. Research indicates that 
bacteria like Abiotrophia spp. and 
Capnocytophaga spp. may 
significantly influence the 
formation of plaque biofilms [13]. 
While this development seems to 
have a robust immunological-
inflammatory foundation, both 
innate (sex and genetic variables) 
and obtained (obesity, stress, 
smoking, concurrent systemic 
disorders) risk determinants 
significantly contribute [14]. Soft 
and hard tissues around the teeth 
experience escalating damage 
from advancing inflammation due 



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to both the direct, deleterious 
health risks associated with 
bacterial virulence factors found in 
dental plaque and the indirect 
consequences of the body's 
heightened, generalized 
inflammatory reaction to 
periodontopathogens [15].  
Inflammation initiates a 
complicated interaction of 
proinflammatory cytokines, nitric 
oxide, matrix metalloproteinases 
(MMPs), prostaglandin E2, and 
various alternative inflammatory 
mediators. Elevated levels of 
tumor necrosis factor alpha (TNF-
α), interleukin-1 beta (IL-1β), IL-6, 
IL-11, and IL-17 facilitate the 
formation of osteoclasts through 
boosting nuclear factor kappa-β 
ligand receptor activator 
expression (RANKL) and 
diminishing osteoprotegerin 
production [11]. Moreover, active 
periodontal lesions demonstrate 
an overproduction of IL-17 and 
RANKL, alongside reduced 
concentrations of anti-
inflammatory cytokines such as IL-
10 and transforming growth factor 
beta1 (TGF-β1), indicating an 
aberrant immunological reaction. 
This disruption in the metabolism 
of bone not solely incline patients 
to periodontal disease but also 
suggests it in the capacity of 
possible risk determinant for 
conditions like rheumatoid 

arthritis, however, agreement is 
still hard to grasp [11,16].  

The Keystone Periodontal 
Pathogen (Porphyromonas 
gingivalis)  

The rod-shaped, Gram-negative, 
anaerobic bacteria known as P. 
gingivalis was identified in 85.75% 
of subgingival plaque in individuals 
with persistent periodontal 
disease [17]. The virulence 
components of P. gingivalis 
include fimbriae, haemolysin, 
hemagglutinins, a capsule, outer 
membrane vesicles, 
lipopolysaccharides, and 
gingipains [18]. The prevalence of 
P. gingivalis correlates with the 
severity of periodontal disease 
and has been recognized by 
researchers as a primary causal 
element in the PD progression. 
The keystone pathogen idea 
suggests that P. gingivalis, even in 
minimal quantities, might trigger 
chronic periodontal disease by 
altering the commensal bacterial 
community, resulting in dysbiosis 
and subsequent disease [19]. 

 Role of Porphyromonas 
gingivalis in Periodontal Disease 

In vivo investigations in mice have 
demonstrated that contagion with 
P. gingivalis induces osteoclastic 
activity [20]. P. gingivalis attaches 
to and infiltrates the epithelial 
layers, proliferates and induces 

periodontal disease. Although the 
epithelium serves as the primary 
obstacle in opposition to 
numerous diseases, including 
periodontal microbiome, P. 
gingivalis infiltrates gingival 
epithelium along with the 
fundamental connective tissues 
[23,24]. It plays a substantial role 
in the etiology of aggressive PD by 
eliciting elevated degrees of pro-
inflammatory cytokines [25]. 
Serotypes K1 and K2 are linked to 
elevated expression of receptor 
activator RANKL. This element 
influences the generation and 
development of osteoclasts and 
triggers a robust T helper1 (Th1) 
and Th17 inflammatory reaction, 
leading to increased breakdown of 
alveolar osseous tissues and 
enhanced destruction of 
periodontal tissue [26]. The 
complement system safeguards 
the host against microbial 
infections via opsonization, 
chemotaxis, and infected cells 
destruction [22]. P. gingivalis 
exhibits resistance to the 
complement system via the 
activity of its enzymes or by 
surface chemicals that enable 
adaptation to the regulatory 
proteins of the host's 
complement. P. gingivalis inhibits 
the cascade process of 
complement component 5 
convertase production within the 
complement system [22,27]. 



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Moreover, complement 
component 3 interacts with P. 
gingivalis fimbriae, facilitating the 
internalization of the bacteria by 
macrophages. P. gingivalis utilizes 
the synergy and crosstalk between 
complement and toll-like 
receptors to alter host defenses 
and evade elimination by the host 
[19]. Levels of complements 
proteins in crevicular fluid are 
diminished in individuals with 
periodontal disease [22,26]. P. 
gingivalis can evade neutrophils 
devastation through diminishing 
their antibacterial and chemotaxis 
efficacy [21,25]. The survival 
mechanisms of P. gingivalis lead to 
a remodeled microbiota, resulting 
in a dysbiotic condition that 
induces inflammatory diseases 
such as periodontal disease [19].  

Rheumatoid Arthritis 

Rheumatoid arthritis is an 
autoimmune, systemic 
inflammatory disorder that 
impacts roughly 1% of the 
population. It is marked by 
persistent joint inflammation, 
destruction of bone and cartilage, 
and systemic extra-articular 
manifestations not directly 
associated with the 
musculoskeletal system [27], 
which occur in a significant 
proportion of patients, resulting in 
poorer disease outcomes [28]. RA 
patients frequently display diverse 

oral manifestations, notably the 
recognized association with 
Sjogren’s syndrome, resulting in 
symptoms such as xerostomia. 
Additional oral concerns 
encompass temporomandibular 
joint abnormalities, methotrexate-
induced ulcers, and an increasing 
emphasis on periodontal disease 
[29].  

Pathogenesis of Rheumatoid 
Arthritis 

       Vulnerability and initiation of 
RA rise from ambient and 
hereditary variables. The most 
often used autoantibodies in 
clinical practice are ACPAs, which 
may be detected in RA patients 
years prior to symptom 
manifestation. Peptidyl arginine 
deiminase (PADI) facilitates the 
post-translational modification 
that transforms arginine or glycine 
residues in normal proteins into 
citrulline, a significant factor 
contributing to the abrogation of 
immunological tolerance in RA 
patients [30].  
Non-resolving inflammation driven 
by aberrantly activated immune 
cells plays a crucial role in the 
development of RA. Immune cells 
penetrate the synovium diffusely; 
however, in some instances, T 
cells and B cells form consolidates, 
with or without follicular dendritic 
cells, leading to the formation of 
lymphoid consolidates or ectopic 

germinal centers [31]. This process 
contributes to the breakdown of 
self-tolerance and accelerates the 
pathogenesis of RA. In RA, the 
majority of proinflammatory 
cytokines originate from 
macrophages and fibroblast-like 
synoviocytes, including IL-1, IL-6 
and TNF-α. TNF-α, a key 
proinflammatory cytokine in RA, 
enhances inflammation by 
activating the NF-κB pathway, 
which promotes osteoclast 
formation [31,32]. IL-1 similarly 
causes fast and powerful 
inflammatory reactions, primarily 
generated by macrophages in RA. 
IL-1 may additionally enhance IL-6, 
IL-8, granulocyte-macrophage 
colony-stimulating factor, 
collagenase, and prostaglandins 
synthesis [31]. Large quantities of 
IL-6 in the synovial fluid of RA 
individuals may additionally 
transmit stimuli of pathogenic 
inflammation in RA- fibroblast-like 
synoviocytes via the Janus kinase 
pathway [33].  

The association between 
rheumatoid arthritis and 
periodontitis 

       The findings from previous 
study have garnered significant 
interest from both Chinese and 
foreign scholars regarding the 
correlation between PD and RA. 
Cantley et al discovered that 
animals afflicted with both PD and 



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RA exhibit more severe RA activity 
and an earlier commencement 
[34]. IL-1 and TNF-α are 
proinflammatory cytokines which 
significantly contribute to the 
pathogenesis of periodontal 
disease and RA. They prompt 
inflammatory cells to infiltrate the 
diseased area, resulting in bone 
degradation through the 
inflammatory mediators secretion 
and cytokines activation, which 
facilitates the breakdown of 
alveolar osseous tissue and 
collagen fibers degradation in 
periodontal disease [35]. Recent 
data demonstrates a substantial 
association between susceptibility 
to RA and the human leukocyte 
antigen DRB1 (HLA-DRB1) genetic 
locus, due to the binding of 
citrullinated self-peptides to HLA-
DR molecules. P. gingivalis, a 
principal microbiome in 
periodontal disease and the only 
recognized human microbiome 
that expresses PADI, is pivotal. 
This enzyme generates 
citrullinated epitopes, which are 
recognized by ACPA in RA [36]. A 
prospective study revealed that 
persons with RA exhibited a 
greater prevalence of periodontal 
disease PD, especially in the midst 
of the individuals with increased 
concentrations of P. gingivalis in 
profound periodontal pockets, in 
comparison to healthy individuals 
[37]. The immunological processes 

resulting in advancing connective 
tissue breakdown and osseous 
tissue resorption, typical of RA, 
are also common in periodontal 
disease. Periodontal disease, a 
contagious ailment predominantly 
induced by bacterial species such 
as P. gingivalis, Aggregatibacter 
actinomycetemcomitans, 
Tannerella forsythia, and 
Treponema denticola, elicits both 
localized and systemic 
immunological reactions. 
Furthermore, the presence of oral 
bacterial DNA and antibodies in 
the synovial fluid and blood of 
patients with RA connect PD with 
the development of RA [11, 16]. A 
potential correlation between PD 
and RA may extend beyond 
causative relationships, 
presumably attributable to 
prevalent genetic and 
environmental risk determinants, 
including major histocompatibility 
class II HLA-DRB1 allele expression 
and tobacco use [11,38]. Although 
the underlying causes differ, 
numerous clinical and public 
health researchers suggest a link 
between RA and PD. Individuals 
with PD have an increased 
susceptibility to RA and vice versa; 
the frequency of PD is twice as 
high in RA individuals in 
comparison to the populace 
[11,37]. Furthermore, RA 
individuals with PD typically 
exhibit a more serious clinical 

progression, irrespective of 
gender, age, smoking or ethnicity 
status, in comparison to 
individuals without RA. Moreover, 
the two illnesses exhibit analogous 
pathways of tissue damage driven 
by inflammatory cells and 
proinflammatory cytokines, 
indicating that periodontal disease 
can contribute to the onset and 
continuation of autoimmune 
inflammatory responses observed 
in RA [11,39]. 

Role of Porphyromonas gingivalis 
in the Development of 
Rheumatoid Arthritis 

       The successful application of 
antibiotics for anaerobic microbial 
infections in RA suggests that 
bacteria may contribute to the 
formation of RA. Identification of 
bacterial DNA from anaerobes and 
elevated antibody titers opposed 
to it in the synovial fluid and 
serum of RA individuals at 
different disease phases supports 
the hypothesis that oral infections 
contribute to the etiology of RA 
[11,40].  
Periodontal pathogens such as P. 
gingivalis can undermine the 
integrity of epithelial tissue, 
infiltrate human endothelial cells, 
and affect transcription and 
protein synthesis, thereby 
facilitating direct systemic entry 
into bloodstream. P. gingivalis can 
infiltrate primary human 



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chondrocytes derived from 
patellar joints, leading to 
prolonged cell cycle advancement 
and heightened programmed cell 
death [11]. P. gingivalis 
synthesizes cysteine 
endopeptidase enzymes which are 
essential for bacterial homeostasis 
and infection mechanisms, 
including amino acids isolation 
from host and the formation of 
fimbriae [11,25]. P. gingivalis 
gingipains facilitate proteolytic 
enzymes activation including 
MMP-1, MMP-3, and MMP-9, 
along with the degradation of 
extracellular matrix host proteins 
such as collagen, fibronectin, and 
laminin. Additionally, gingipains 
induce the degradation of 
complement factors and enhance 
the permeability of blood vessels 
[11,41]. The pathogenesis of RA is 
associated with the involvement 
of P. gingivalis in the process of 
citrullination. Proteins experience 
a post-translational modification 
known as citrullination, converting 
arginine residues into citrulline 
[8,42]. The bacterium produces 
enzymes, including PADI, catalyze 
citrullination. The infection elicits 
immunological reaction which can 
lead to systemic consequences. 
Citrullination is a pivotal process in 
the pathogenesis of RA, as it 
generates antibodies against 
citrullinated proteins [8,43]. The 
citrullination mediated by P. 

gingivalis may facilitate the 
production of ACPAs, establishing 
a connection between periodontal 
disease and the onset or 
worsening of RA. Citrullinated 
proteins are commonly present in 
the synovial fluids of people with 
RA. The existence of P. gingivalis 
and its citrullination role inside of 
the mouth may affect the systemic 
dissemination of citrullinated 
peptides, intensifying synovial 
inflammation in predisposed 
people [36,43].  

Conclusion  

       The growing body of evidence 
linking periodontitis, particularly 
the role of P. gingivalis, to the 
development and exacerbation of 
RA highlights the complex 
interactions between oral and 
systemic health. Periodontitis, a 
chronic inflammatory disease, is 
associated with a range of 
systemic conditions, with RA being 
one of the most compelling 
examples of such connections. The 
key periodontal pathogen P. 
gingivalis plays a central role in 
this relationship, not only by 
inducing local inflammation and 
bone resorption in the oral cavity 
but also by influencing systemic 
immune responses through 
mechanisms such as citrullination. 
P. gingivalis secretes PADI, an 
enzyme that catalyzes the 
conversion of arginine to citrulline, 

a critical process that generates 
autoantibodies against 
citrullinated proteins, a hallmark 
of RA. This molecular interaction 
suggests that oral bacteria may 
directly contribute to the immune 
dysregulation observed in RA, 
leading to the production of ACPA 
and the subsequent development 
of chronic joint inflammation. 
Additionally, the shared 
inflammatory mediators and 
cytokine profiles between PD and 
RA further reinforce the potential 
for a bidirectional relationship, 
where one condition may 
influence the progression of the 
other. 

Given the significant prevalence of 
periodontitis worldwide, and the 
established connection between 
periodontal disease and RA, there 
is a pressing need for further 
research into the underlying 
mechanisms of this association. 
Understanding how P. gingivalis 
and other periodontal pathogens 
contribute to RA may offer new 
avenues for preventive and 
therapeutic strategies, not only 
targeting oral health but also the 
systemic inflammatory pathways 
involved in autoimmune diseases 
like RA. Integrating periodontal 
care into the management of RA 
could potentially improve patient 
outcomes and reduce disease 
severity, highlighting the 
importance of early detection and 



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comprehensive treatment 
strategies that address both oral 
and systemic health. 

Funding  

Self-funded. 

Conflict of Interest  

The authors declare no conflict of 
interest. 

References 

1. Martínez-García M, 
Hernández-Lemus E. 
Periodontal inflammation 
and systemic diseases: an 
overview. Frontiers in 
physiology. 2021 Oct 
27;12:709438. 

2. Jahid M, Khan KU, Ahmed 
RS. Overview of rheumatoid 
arthritis and scientific 
understanding of the 
disease. Mediterranean 
Journal of Rheumatology. 
2023;34(3):284-91. 

3. Lopez-Oliva I, Malcolm J, 
Culshaw S. Periodontitis 
and rheumatoid arthritis—
Global efforts to untangle 
two complex diseases. 
Periodontology 2000. 2024 
Feb 27. 

4. Abdullah WL, Al-Hashimy 
AF, Al-Ghurabi BH. Role of 
salivary caspase-1 and 
gasdermin D in the 

pathophysiology of 
rheumatoid arthritis in 
relation to salivary pH and 
flow rate of saliva. World 
Academy of Sciences 
Journal. 2024 Nov 18;7(1):7. 

5. Al-Daragi FZ, Al-Ghurabi BH, 
Abdullah NN. Serum levels 
of antimicrobial peptides 
(Cathelicidins and Beta 
Defensins-1) in patients 
with periodontitis. Journal 
of Baghdad College of 
Dentistry. 2024 Mar 
15;36(1):9-18. 

6. Jain N, Dutt U, Radenkov I, 
Jain S. WHO's global oral 
health status report 2022: 
Actions, discussion and 
implementation. Oral 
diseases. 2024 
Mar;30(2):73-9. 

7. Chen MX, Zhong YJ, Dong 
QQ, Wong HM, Wen YF. 
Global, regional, and 
national burden of severe 
periodontitis, 1990–2019: 
An analysis of the Global 
Burden of Disease Study 
2019. Journal of clinical 
periodontology. 2021 
Sep;48(9):1165-88. 

8. Kwon T, Lamster IB, Levin L. 
Current concepts in the 
management of 
periodontitis. International 

dental journal. 2021 Dec 
1;71(6):462-76. 

9. Al-Ghurabi BH, Adham ZS, 
Abbas AA: Level of β-
defensin among Iraqi 
patients with COVID-19 in 
relation to oral health 
status. J Emerg Med 
Trauma Acute Care. 2022; 
2022(3): 2.  

10.  Al-Ghurabi BH. The Role of 
Soluble TLR-2 in the 
Immunopathogenesis of 
Gingivitis. International 
Medical Journal. 2021 Jun 
2;28(1):37-9. 

11. Krishna AS, Ahalya U, 
Dharan SS, Amal A. 
Unraveling the Interplay: 
Periodontitis and 
Rheumatoid Arthritis. 
International Journal of 
Tropical Medicines. 
2024;1(1):31-9p 

12. Mahmood HK, AL-Ghurabi 
BH. Association between 
anti-CMV IgG and salivary 
levels of IL-6 and TNF-α in 
chronic periodontitis. J 
Bagh Coll Dent. 
2020;32(2):5-11.  

13. Li X, Yu C, Zhang B, Shan X, 
Mao W, Zhang Z, Wang C, 
Jin X, Wang J, Zhao H. The 
recovery of the microbial 
community after plaque 



Poten&al Role of Periodontopathogens in Rheumatoid Arthri&s   
 

Vol 13 No 1 (2025)    DOI 10.5195/d3000.2025.808 

 h#p://den*stry3000.pi#.edu 

removal depends on 
periodontal health status. 
npj Biofilms and 
Microbiomes. 2023 Oct 
7;9(1):75. 

14.  Di Spirito F, Di Palo MP, 
Rupe A, Piedepalumbo F, 
Sessa A, De Benedetto G, 
Russo Barone S, Contaldo 
M. Periodontitis in Psoriatic 
Patients: Epidemiological 
Insights and Putative 
Etiopathogenic Links. 
Epidemiologia. 2024 Jul 
26;5(3):479-98. 

15. Gao L, Kang M, Zhang MJ, 
Reza Sailani M, Kuraji R, 
Martinez A, Ye C, Kamarajan 
P, Le C, Zhan L, Rangé H. 
Polymicrobial periodontal 
disease triggers a wide 
radius of effect and unique 
virome. npj Biofilms and 
Microbiomes. 2020 Mar 
10;6(1):10. 

16.  Krutyhołowa A, Strzelec K, 
Dziedzic A, Bereta GP, 
Łazarz-Bartyzel K, Potempa 
J, Gawron K. Host and 
bacterial factors linking 
periodontitis and 
rheumatoid arthritis. 
Frontiers in immunology. 
2022 Aug 25;13:980805. 

17. Xu W, Zhou W, Wang H, 
Liang S. Roles of 
Porphyromonas gingivalis 

and its virulence factors in 
periodontitis. Advances in 
protein chemistry and 
structural biology. 2020 Jan 
1;120:45-84. 

18. Aleksijević LH, Aleksijević 
M, Škrlec I, Šram M, Šram 
M, Talapko J. 
Porphyromonas gingivalis 
virulence factors and clinical 
significance in periodontal 
disease and coronary artery 
diseases. Pathogens. 2022 
Oct 11;11(10):1173. 

19.  Huang X, Li Y, Zhang J, Feng 
Q. Linking Periodontitis with 
Inflammatory Bowel 
Disease through the Oral–
Gut Axis: The Potential Role 
of Porphyromonas 
gingivalis. Biomedicines. 
2024 Mar 19;12(3):685.  

20. Zhou N, Zou F, Cheng X, 
Huang Y, Zou H, Niu Q, Qiu 
Y, Shan F, Luo A, Teng W, 
Sun J. Porphyromonas 
gingivalis induces 
periodontitis, causes 
immune imbalance, and 
promotes rheumatoid 
arthritis. Journal of 
leukocyte biology. 2021 
Sep;110(3):461-73. 

21. Zheng S, Yu S, Fan X, Zhang 
Y, Sun Y, Lin L, Wang H, Pan 
Y, Li C. Porphyromonas 
gingivalis survival skills: 

Immune evasion. Journal of 
periodontal research. 2021 
Dec;56(6):1007-18. 

22. Kareem HH, Al-Ghurabi BH, 
Albadri C. Molecular 
detection of 
Porphyromonas gingivalis in 
COVID-19 Patients. Journal 
of Baghdad College of 
Dentistry. 2022 Jun 
15;34(2):52-61. 

23. Neurath N, Kesting M. 
Cytokines in gingivitis and 
periodontitis: from 
pathogenesis to therapeutic 
targets. Frontiers in 
Immunology. 2024 Aug 
26;15:1435054.  

24. Melgar-Rodríguez S, 
Polanco A, Ríos-Muñoz J, 
García M, Sierra-Cristancho 
A, González-Osuna L, Díaz-
Zúñiga J, Carvajal P, Vernal 
R, Bravo D. Differential 
Response of Human 
Dendritic Cells upon 
Stimulation with 
Encapsulated or Non-
Encapsulated Isogenic 
Strains of Porphyromonas 
gingivalis. International 
Journal of Molecular 
Sciences. 2024 Apr 
20;25(8):4510.  

25. Chen WA, Dou Y, Fletcher 
HM, Boskovic DS. Local and 
systemic effects of 



Poten&al Role of Periodontopathogens in Rheumatoid Arthri&s   
 

Vol 13 No 1 (2025)    DOI 10.5195/d3000.2025.808 

 h#p://den*stry3000.pi#.edu 

Porphyromonas gingivalis 
infection. Microorganisms. 
2023 Feb 13;11(2):470. 

26. Ali, A. F. and Taha, G. I. 
2024. Gingival crevicular 
fluid volume and protein 
concentration: A biomarker 
tool for predicting 
periodontal diseases 
progression and severity. 
Natural and Life Sciences 
Communications.23(4): 
e2024055.  

27. Figus FA, Piga M, Azzolin I, 
McConnell R, Iagnocco A. 
Rheumatoid arthritis: extra-
articular manifestations and 
comorbidities. 
Autoimmunity reviews. 
2021 Apr 1;20(4):102776. 

28. González DA, Bianchi ML, 
Armada M, Escalante AC, 
Salgado PA, Seni S, Citera G, 
Ferrary T, Orman B. 
Hyposalivation and 
periodontal disease as oral 
non-articular characteristics 
in rheumatoid arthritis. 
Clinical Rheumatology. 
2024 Jan;43(1):95-102. 

29. Benli M, Batool F, Stutz C, 
Petit C, Jung S, Huck O. 
Orofacial manifestations 
and dental management of 
systemic lupus 
erythematosus: A review. 

Oral diseases. 2021 
Mar;27(2):151-67. 

30. Sokolova MV, Schett G, 
Steffen U. Autoantibodies in 
rheumatoid arthritis: 
historical background and 
novel findings. Clinical 
reviews in allergy & 
immunology. 2022 
Oct;63(2):138-51. 

31. Gao Y, Zhang Y, Liu X. 
Rheumatoid arthritis: 
pathogenesis and 
therapeutic advances. 
MedComm. 2024 
Mar;5(3):e509. 

32. Ding Q, Hu W, Wang R, 
Yang Q, Zhu M, Li M, Cai J, 
Rose P, Mao J, Zhu YZ. 
Signaling pathways in 
rheumatoid arthritis: 
implications for targeted 
therapy. Signal transduction 
and targeted therapy. 2023 
Feb 17;8(1):68. 

33. Su J, Li S, Chen J, Jian C, Hu 
J, Du H, Hai H, Wu J, Zeng F, 
Zhu J, Liu Y. 
Glycerophospholipid 
metabolism is involved in 
rheumatoid arthritis 
pathogenesis by regulating 
the IL-6/JAK signaling 
pathway. Biochemical and 
Biophysical Research 
Communications. 2022 Apr 
16;600:130-5. 

34. Xiao F, Li C, Lin Y, Peng Z, Xu 
X, Wen Y, Huang N, Zhang 
P. Increased risk of 
periodontitis occurrence in 
patients with rheumatoid 
arthritis and its association 
with the levels of IL-1β and 
TNF-α in gingival crevicular 
fluid. Annals of Palliative 
Medicine. 2021 
Aug;10(8):9078087-9087. 

35. Luo P, Wang P, Xu J, Hou W, 
Xu P, Xu K, Liu L. 
Immunomodulatory role of 
T helper cells in rheumatoid 
arthritis: a comprehensive 
research review. Bone & 
joint research. 2022 Jul 
20;11(7):426-38. 

36. Renvert S, Berglund JS, 
Persson GR, Söderlin MK. 
The association between 
rheumatoid arthritis and 
periodontal disease in a 
population-based cross-
sectional case-control 
study. BMC rheumatology. 
2020 Dec;4:1-8. 

37. Li Y, Guo R, Oduro PK, Sun 
T, Chen H, Yi Y, Zeng W, 
Wang Q, Leng L, Yang L, 
Zhang J. The relationship 
between porphyromonas 
gingivalis and rheumatoid 
arthritis: a meta-analysis. 
Frontiers in cellular and 
infection microbiology. 
2022 Jul 18;12:956417. 



Poten&al Role of Periodontopathogens in Rheumatoid Arthri&s   
 

Vol 13 No 1 (2025)    DOI 10.5195/d3000.2025.808 

 h#p://den*stry3000.pi#.edu 

38. Möller B, Kollert F, Sculean 
A, Villiger PM. Infectious 
triggers in periodontitis and 
the gut in rheumatoid 
arthritis (RA): A complex 
story about association and 
causality. Frontiers in 
immunology. 2020 Jun 
3;11:1108. 

39. Zekeridou A, Gilbert B, 
Finckh A, Giannopoulou C. 
Periodontitis in first degree-
relatives of individuals with 
rheumatoid arthritis: a 
short narrative review. 
Frontiers in Oral Health. 
2022 May 6;3:895753. 

40. Ermencheva P, Kotov G, 
Shumnalieva R, Velikova T, 
Monov S. Exploring the Role 
of the Microbiome in 
Rheumatoid Arthritis—A 
Critical Review. 
Microorganisms. 2024 Jul 
9;12(7):1387. 

41. Chow YC, Yam HC, 
Gunasekaran B, Lai WY, Wo 
WY, Agarwal T, Ong YY, 
Cheong SL, Tan SA. 
Implications of 
Porphyromonas gingivalis 
peptidyl arginine deiminase 
and gingipain R in human 
health and diseases. 
Frontiers in Cellular and 
Infection Microbiology. 
2022 Sep 29;12:987683. 

42. Kwon EJ, Ju JH. Impact of 
posttranslational 
modification in 
pathogenesis of rheumatoid 
arthritis: focusing on 
citrullination, 
carbamylation, and 
acetylation. International 
journal of molecular 
sciences. 2021 Sep 
30;22(19):10576. 

43. Pérez-Pérez ME, Nieto-
Torres E, Bollain-y-Goytia JJ, 
Delgadillo-Ruíz L. Protein 
Citrullination by Peptidyl 
Arginine 
Deiminase/Arginine 
Deiminase Homologs in 
Members of the Human 
Microbiota and Its 
Recognition by Anti-
Citrullinated Protein 
Antibodies. International 
Journal of Molecular 
Sciences. 2024 May 
10;25(10):5192.