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Oral diagnostics - Focal infection .pptx
1. Influence of oral inflammatory
diseases on the systemic conditions
Peter Valyi DMD, PhD
2. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Main chapters
• Importance of the topic, historical background
• Definition
• Pathogenesis
• Diseases
3. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Historical background
4. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Importance of this topic
• Cardiovascular diseases (CVDs) are the leading cause of death globally.
An estimated 17.9 million people died from CVDs in 2019, representing
32% of all global deaths. Of these deaths, 85% were due to heart attack
and stroke.
• The cost of circulatory diseases to the EU economy was estimated at
EUR 210 billion in 2015, of which slightly more than half was due to direct
health care costs. The final 2015 EU Budget of EUR 141.3 billion
• Prevalence of DM in 20-79 years old population in the OECD countries
~7% ( ~ 85 millió fő)
• Medication used in DM has doubled over the past few years.
5. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Historical background
• Hippocrates – in ancient Greece, had reported cure of an arthritis
case by tooth extraction
• Miller WD: The human mouth as a focus of infection. Dental Cosmos 1891;
33:689-713
• Hunter W: „Oral sepsis” Role of sepsis and antisepsis in medicine. Lancet
1911; 1: 79-86
6. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Historical background
• Billings: „Focal infection”
Billings F.: Chronic focal infections and their aetiologic relations to arthritis and
nephritis. Arch Intern Med. 1912; 9: 484-489
• Mayo CH: advocated extraction of known healthy teeth to prevent
focal infection
Mayo CH: Focal infection of dental origin. Dental Cosmos 1922; 64: 1206-
1208
7. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Historical background
• Host-parasite interaction
• Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A
summary of current work. Lab Invest. 1976; 34:235–249
• New methods in the periodontal science (molecular biology, epidemiology,
etc.)
• Exploring of molecular aspects of periodontitis and systemic diseases
8. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Definitions
9. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
„Focal infection”
• Focal Infection Theory – An acute or chronic infection in which bacteria are
localized in some region of the body, as the tonsils or the periodontal tissue, from
which they or their metabolites or toxines may spread to some other organ or
structure of the body causing secunder diseases
[Roberts HL (1921). Focal infection. Br J Dermatol 33, 353–373]
• Three mechanisms or pathways linking oral infections to secondary systemic
manifestations have been suggested:
1. Metastatic infection from the oral cavity due to transient bacteremia;
2. Metastatic injury due to oral microbial toxins;
3. Metastatic inflammation due to immunologic injury caused by oral microorganisms
• Septic conditions due to oral infection: transient bacteremia - hematogenous
spread of infection, spread into deep fascial space, lymph vessels, - secondary
infections from odontogenic origin
10. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Secondary infections from odontogenic
origin
• Head and neck and mediastinum
• Sinusitis
• Mediastinitis (descending necrotizing); empyema, pericarditis
• Face-neck: superficial and deep infections (phlegmone)
• Spreading: deep fascial space
• Ethmoid sinus infection
• Cavernous sinus thrombosis
• Endophtalmitis
• Brain abscess, meningitis, paraspinal abscess
11. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontal medicine
The World Workshop in Periodontics (1996): „Periodontal medicine”
• Branch of periodontology focusing on the wealth of new data establishing
a strong relationship between periodontal health or disease and systemic
health or disease.
• This means a two-way relationship in which periodontal disease in an individual may
be a powerful influence on an individual’s systemic health or disease as well as the
more customarily understood role that systemic disease may have in influencing an
individual’s periodontal health or disease.
[Offenbacher S (1996). Periodontal diseases: pathogenesis. Ann Periodontol 1, 821–878]
12. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Endodontic medicine
Segurea-Egea et al – IEJ 2015 - evaluating the association between
endodontic and systemic diseases
• Chronic periodontal and endodontic inflammatory processes have three
important similarities
• Both are chronic infections of the oral cavity
• Both are polymicrobial infections sharing a common microbiota with a predominance
of Gram-negative anaerobic bacteria
• Elevated cytokine levels may be released systemically from acute and chronic
manifestations of both disease processes, for example increased concentrations of
inflammatory mediators have been detected both in the gingival crevicular fluid of
subjects with PD and in the periapical tissues of endodontically involved teeth
13. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Pathogenesis
14. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Evidencies
• Epidemiologic studies
• Clinical trials
• Human in-vitro studies
• Animal studies
• Meta-analysis
15. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontal diseases
• More than 50% of population of EU suffer from periodontitis, more than 10%
are severe cases
• Prevalence in the 60-65 old population: 70-85%
16. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontitis
• Periodontopathogens – in the biofilm
• Invade to the pocket wall
• Inflammation – host response
Rossa C, Kirkwood KL: Molecular
biology of host-microbe interaction in:
Newman MG, Takei HH, Klokkevold
PR, Carranza FA: Carranza’s Clinical
Periodontology 12th ed, 2015
17. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontitis
MAMP
(microbial-associated molecular pattern)
PRR
(pattern-recognition receptors)
Pro-inflammatory cytokins
Anti-inflammatory cytokins
Growth factors
Enzymes
Activation of multiple signaling
pathways
Inflammation
Innate host
response
Trained
host response
18. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontitis
MAMP
(microbial-associated molecular pattern)
PRR
(pattern-recognition receptors)
Resident microorganisms Pathogen microorganizms
Antimicrobial proteins
+ IL-8
Antimicrobial proteins Host
response
19. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Local and systemic mechanisms
linking periodontal disease and
inflammatory comorbidities
20. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Conceptual model illustrating the ways in which
periodontal infection affects the human body
Borgnakke WS, Dent Clin North Am, 59 (2015) 885-917
• Bacteremia – direct effect
• Inflammatory response –
indirect effect
• Immune response –
indirect reaction
21. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Inflammation
• Periodontitis – systemic inflammation (low-grade)
• Increased level of pro-inflammatory mediators: IL-1, IL-6, CRP, Fibrinogen
• Cause of inflammation:
• Bacteremia – microorganisms and their byproducts (LPS, proteases) hematogen
dissemination to the target tissues:
• via circulation
• trafficking by dendritic cells, cardiovascular cells – dissemination to the endothelia by cell-to-cell
contact - intracellular survival
• Pro-inflammatory mediators from the periodontal tissue – hematogen dissemination
• Penetration:
• Through ulceration of inflammed pocket epithelium (8-20 cm2)
• Inhalation: Mouth – mucosa of airways
• Ingestion: Mouth – mucosa of gastrointestinal tract
• Microorganisms have developed sophisticated ways to survive the host defense system
• When they reach an invited location they make a landing and multiply
22. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Host response
• Periodontal pathogens induce systemic host response
• A quantitative analysis of serum antibodies against
periodontopathogens demonstrated significantly increased levels in
periodontitis patients as compared to controls
• Systemic inflammation – systemic metabolic-immun reactions result in
elevated total load of systemic inflammatory responses
• LDL (low-density lipoprotein), triglycerides – elevated
• HDL – reduced levels
23. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Host response - evidences
• The association of periodontitis, obesity, dyslipidaemia, T2DM,
NAFLD/NASH and CVD might be attributed, in part, to causal
relationships, as suggested by clinical interventions
• Effective periodontal treatment reduces systemic inflammatory markers and
favourably influences the metabolic status of patients with T2DM (who showed
reduction of plasma glucose concentrations and HbA1c), as well as leading to
improvements in vascular and kidney functions
• Periodontal treatment of patients with periodontitis who are hyperlipidaemic reduces
LDL and triglyceride levels and increases HDL levels
• Periodontal treatment of patients with NAFLD/NASH decreases the serum levels of
hepatic–parenchymal damage markers, aspartate aminotransferase and alanine
aminotransaminase, and in patients with cirrhosis, periodontal treatment reduces
local and systemicinflammation and endotoxaemia, as well as improving cognitive
function and quality of life in those with prior hepatic encephalopathy
24. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Host response
• Cross-reactivity between bacterial cells with endothelial cells
• Antibodies against human HSP 60 and antibodies against Porphyromonas gingivalis
(GroEL) in sera and inflamed gingival tissues were found in periodontitis patients.
Molecular mimicry between GroEL of the periodontopathic Porphyromonas gingivalis
and autologous human HSP 60 may play a role in immune mechanisms. The
extensive homology between human and bacterial HSPs may play a role in the
activation of atherosclerotic changes. The binding of antibodies to the endothelium
surface may be a triggering mechanism of inflammatory autoimmunity disease
Bartova et al: Periodontitis as a risk factor of atherosclerosis J Immunol Res 2014;
2014:636893
25. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Host response - Trained myelopoiesis in the bone marrow
• Periodontitis-associated bacteraemias and systemic inflammation bone
marrow HSC
• Increased proliferation and myeloid differentiation leading to enhanced myelopoiesis
• Systemic infections and inflammations can be sensed in the bone marrow by haematopoietic stem and progenitor cells
(HSPCs) via Toll-like receptors (TLRs) or receptors for inflammatory cytokines
• increased production of cells that fight infections, such as neutrophils and monocytes
• Through further differentiation via macrophage colony-stimulating factor (M-CSF) and receptor activator of
NF-κB ligand (RANKL), the monocytic lineage is the precursor of osteoclasts, which are giant multinucleated
bone-resorbing cells
• „Trained-myelopoiesis-acquired immunity”
26. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Host response - Trained myelopoiesis in the bone marrow
• Systemic inflammation bone marrow
• peripheral blood neutrophils or monocytes from patients with periodontitis respond with
higher pro-inflammatory cytokine production than the same cell types from healthy
individuals – hyper-reactivity
• this hyper-reactivity often remains even after successful periodontal therapy; that is, the
higher capacity to produce cytokines seen in myeloid cells from patients versus healthy
controls persists after therapy for at least 2 months
• periodontitis affects haematopoietic tissue activity - this trained state of peripheral
myeloid cells might be the result of long-term epigenetic immune memory imprinted in
inflammation-adapted HSPCs in the bone marrow
27. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Trafficking of orally primed inflammatory cells
„Lymphocyta-trafficking”, „Myeloid cell trafficking”
• Specifically, oral pathobiont-specific T cells (mostly Th17), which expand
during periodontitis, express the gut-homing molecules (CC-chemokine
receptor 9 - CCR9 and α4β7 integrin: the receptor for the gut-specific
vascular addressin MAdCAM1) and migrate from the oral cavity - draining
cervical lymph nodes to the gut proliferate and exacerbate colitis
• mucosal immune system is an integrated, system-wide organ:
• respiratory influenza infection in mice results in intestinal immune injury attributed to the
recruitment of CCR9+CD4+ T cells from the lungs. The lung-derived transmigrated T cells
caused intestinal dysbiosis and inflammation by secreting IL-17A and IFNγ. Although not
all individuals with flu, or other respiratory infections, develop diarrhoea or other
gastroenteritis symptoms, this mechanism might contribute to those substantial cases
presenting with both respiratory and gastroenteritis symptoms, as seen in many patients
with COVID-19
28. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Trafficking of orally primed inflammatory cells
„Lymphocyta-trafficking”, „Myeloid cell trafficking”
• Blood-borne P. gingivalis is taken up by human blood (CD1c+CD209+)
myeloid dendritic cells (mDCs) and carrying mDCs in atheromatous plaques
• Human monocyte-derived DCs that have internalized P. gingivalis acquire enhanced pro-
inflammatory and atherogenic potential
• The microbial cargo of P. gingivalis-carrier blood mDCs contains additional species
(Burkholderia cepacia, Helicobacter pylori, Pseudomonas spp., Moraxella catarrhalis, K.
pneumoniae and Salmonella enterica). Therefore, additional species, not necessarily of
oral origin, might contribute to the pathological reprogramming of these cells –
periodontitis-associated pathogens are likely important for their altered pathogenic
potential
29. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periapical lesions – Apical periodontitis (AP)
• In Europe, the prevalence of AP is as high as 34–61% of individuals and
2.8–4.2% of the teeth(Jimenez-Pinzon et al. 2004, Lopez-Lopez et al.
2012)
• The prevalence of AP increases with age (Eriksen 1998)
• Radiographic evidence of persistent chronic AP in 24–65% of root filled
teeth (Jimenez-Pinzon et al. 2004, Lopez-Lopez et al. 2012)
30. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Interrelationship between endodontics and
systemic pathological conditions
• Systemic disease – susceptibility
to infection
• AP – local inflammation and bone
resorption, MO proliferation:
bacterial endotoxins, exotoxins to
the bloodstream
• Triggering an systemic host
response, pro-inflammatory
cytokins, dysregulation
31. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Target tissues - comorbidities
• Cardiovascular diseases
• Diabetes mellitus
• Lung diseases
• Infertility – Adverse pregnancy outcomes
• Rheumatoid arthritis
• Inflammatory bowel diseases
• Colorectal cancer
• Alzheimer’s-diseases
• Others
32. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Comorbidities
33. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Cardiovascular diseases
34. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Cardiovascular diseases
• Bacteremia
• Daily activities, invasive dental procedures – transient bacteremia
• Infective endocarditis (IE) – colonization of the endocardial layer and destruction of
heart tissues, such as valves, by oral bacteria
• Prophylaxis (AHA-from 1960-)
35. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Cardiovascular diseases
• Bacteremia
• Periodontal bacteria are able to invade both human coronary artery endothelial cells and
coronary artery smooth muscle cells, so persons with periodontal infection have greater
risk of myocardial infarction
Dorn BR, Dunn WA Jr, Progulske-Fox A. Invasion of human coronary artery cells by periodontal pathogens. Infect
Immun 1999;67(11):5792–8.
• Several reports have found periodontal bacteria in atheromatous plaque
Haraszthy VI, Zambon JJ, Trevisan M, et al. Identification of periodontal pathogens in atheromatous plaques. J
Periodontol 2000;71(10):1554–60.
• Periodontal bacteria most likely can contribute to destabilization of atherosclerotic plaque
Range H, Labreuche J, Louedec L, et al. Periodontal bacteria in human carotid atherothrombosis as a potential
trigger for neutrophil activation. Atherosclerosis 2014;236(2):448–55.
• P gingivalis infection is associated with aortic aneurysms and with proliferation of smooth
muscle cell tissue in developing aneurysms
Wada K, Kamisaki Y.: Roles of oral bacteria in cardiovascular diseases – from molecular mechanisms to clinical
cases: involvement of Porphyromonas gingivalis in the development of human aortic aneurysm. J Pharmacol Sci
2010;113(2):115–9
36. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Vascular damage - model
Hajishengallis G and Chavakis T:
Local and systemic mechanisms linking periodontal disease and
inflammatory comorbidities
Nat Rev Immunol. 2021 Jan 28:1-15
vascular endothelial barrier disruption and increased permeability by disrupting intercellular junctions
37. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Cardiovascular diseases
• Potential role of systemic inflammation
• Inflammation, manifested by the general acute phase
inflammatory biomarker C-reactive protein (CRP), is an
important risk factor for a first thrombotic event (myocardial
infarction or ischemic stroke Ridker et al 1997
• CRP, which has been shown to be elevated in patients with
periodontitis, might be more important than low-density
cholesterol levels as a cause of atherosclerosis. Ridker és
Silverton, 2008
38. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Cardiovascular diseases
• Potential role of systemic inflammation
• Inflammation actually precedes calcification of the arterial wall in atherogenesis
Abdelbaky A, et al.: Focal arterial inflammation precedes subsequent calcification in the same location: a longitudinal FDG-
PET/CT study. Circ Cardiovasc Imaging 2013;6(5):747–54.
• Periodontal disease that is inflammatory in nature is recognized as an independent risk
factor for atherosclerosis, regardless of other risk factors.
Kebschull M, et al.: Mobilization of endothelial progenitors by recurrent bacteremias with a periodontal pathogen. PLoS One
2013;8(1): e54860.
Katsiki N, et al.: Should we expand the concept ofcoronary heart disease equivalents? Curr Opin Cardiol 2014;29(4):389–95.
• Never-smokers with periodontal disease were found to have a 43% higher risk of
experiencing another fatal or nonfatal cardiovascular event than such individuals without
periodontal disease
Dorn JM, Genco RJ, Grossi SG, et al. Periodontal disease and recurrent cardiovascular events in survivors of myocardial
infarction (MI): the Western New York Acute MI study. J Periodontol 2010;81(4):502–11.
• In Japanese and US participants with clinical echocardiograms, 77% had cardiac
calcifications and 51% had moderate to severe periodontitis
Pressman GS, et al.: Periodontal disease is an independent predictor of intracardiac calcification. Biomed Res Int
2013;2013:854340.
39. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Diabetes mellitus
40. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Diabetes mellitus → Periodontitis
• Periodontitis severity and extent was associated with both newly diagnosed
prediabetes and diabetes
Lamster IB, et al. Periodontal findings in individuals with newly identified prediabetes or diabetes mellitus. J Clin
Periodontol 2014; 41(11):1055–60.
• The periodontal breakdown in prediabetes ranged between that in persons
with normal blood sugar levels and those with overt diabetes, suggesting
hyperglycemia as potentially causing the periodontal damage even before the
diagnosis of prediabetes. Persons with prediabetes had worse clinical
periodontal health, radiographic bone loss, and self-reported oral health
(gingival bleeding, chewing pain, dry mouth, and burning mouth) than
individuals with normal glycemic levels
Javed F, et al. Effect of nonsurgical periodontal therapy (with or without oral doxycycline delivery) on glycemic
status and clinical periodontal parameters in patients with prediabetes: a short-term longitudinal randomized
case-control study. Clin Oral Investig 2014;18(8):1963–8.
41. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Periodontitis → Diabetes mellitus
The effect of periodontal infection on DM:
• Bacteria from the periodontium cause general
inflammation in the body - Overexpression of
cytokines:
• Inflammation weakens the action of insulin (insulin
resistance)
• Inflammation reduces the production of insulin in the
pancreas - Damage of -cell
Sugar builds up in the blood (hyperglycemia)
Formation of long-term blood sugar (HbA1c) happens
because of the high sugar concentration in the blood
(hyperglycemia).
42. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Diabetes mellitus - AP
• Effect of DM on AP
(Segura-Egea et al, 2019)
43. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Diabetes mellitus - AP
• Effect of AP on glycemic
control (Segura-Egea et al,
2019)
44. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Respiratory tract diseases
45. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Respiratory tract diseases
• Aspiration pneumonia (HAP – Hospital-acquired Pneumonia)
• Bacteria from dental plaque are associated with pneumonia
Heo SM, et al. Genetic relationships between respiratory pathogens isolated from dental plaque and
bronchoalveolar lavage fluid from patients in the intensive care unit undergoing mechanical ventilation. Clin Infect
Dis 2008;47(12):1562–70.
• Patients with periodontitis have more than a 3-fold higher risk of having lower respiratory
tract infection than those without periodontitis among hospital patients
Gomes-Filho IS, et al. Periodontitis and nosocomial lower respiratory tract infection: preliminary findings. J Clin
Periodontol 2009;36(5): 380–7.
• Among nursing home residents, those without oral health care have 3.6 times higher
mortality from pneumonia than those who were assigned oral hygiene care by nursing
assistants
Bassim CW, et al. Modification of the risk of mortality from pneumonia with oral hygiene care. J Am Geriatr Soc
2008;56(9):1601–7.
46. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Respiratory tract diseases
• Ventilator-assisted pneumonia
• effective oral health care is important for adult patients in intensive care, and the use
of either mouth rinse or gel that contains chlorhexidine is associated with a 40%
decrease in the risk of developing ventilator-assisted pneumonia
Shi Z, Xie H, Wang P, et al. Oral hygiene care for critically ill patients to prevent ventilator-associated
pneumonia. Cochrane Database Syst Rev 2013;(8):CD008367. [Systematic review/meta-analysis].
47. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Respiratory tract diseases
• COPD
• Development of COPD strongly association with
• Poor periodontal conditions
• Frequency of professional dental care
• Knowledge about oral health
Liu Z, et al. Oral hygiene, periodontal health and chronic obstructive pulmonary disease exacerbations. J Clin
Periodontol 2012;39(1): 45–52.
Wang Z, et al. Periodontal health, oral health behaviours, and chronic obstructive pulmonary disease. J Clin
Periodontol 2009;36(9): 750–5.
48. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Pregnancy
49. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Adverse effect of pregnancy
• Periodontal infection association with:
• Pre-eclampsia (hypertensio, protein in the urine, organ damage)
Sgolastra F, Petrucci A, Severino M, et al. Relationship between periodontitis and pre-eclampsia: a meta-
analysis. PLoS One 2013;8(8):e71387 [Systematic review/meta-analysis].
Wei BJ, Chen YJ, Yu L, et al. Periodontal disease and risk of preeclampsia: a meta-analysis of observational
studies. PLoS One 2013;8(8):e70901 [Systematic review/meta-analysis].
• Pre-term birth and/or low birth weight
Prof. Dr. Gorzó István
Prof. Dr. Radnai Márta
50. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Rheumatoid arthritis
51. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Rheumatoid arthritis - mechanisms
• Periodontitis – Invasion of periodontopathogen
into the pocket wall:
• bacteremia
• systemic inflammation
• P. gingivalis – increased IL-6 in sera – myeloid
effect: osteoclast precursors transitions where –
osteoclastogenesis induced by RANKL –
produce by osteoblasts (stimulated by IL-17
from Th17 helper cells): bone resorptions
Ábra: Hajishengallis G and Chavakis T:
Local and systemic mechanisms linking periodontal disease and
inflammatory comorbidities
Nat Rev Immunol. 2021 Jan 28:1-15
52. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Rheumatoid arthritis
• Identification of periodontal bacterial DNA by PCR in subgingival dental plaque,
serum and synovial fluid of patient with rheumatoid arthritis and periodontal
disease patients
Martinez-Martinez R.E., Abud-Mendoza C., Patino-Marin N., Rizo-Rodriguez J.C., Little J.W., Loyola-
Rodriguez J.P. Detection of periodontal bacterial DNA in serum and synovial fluid in refractory
rheumatoid arthritis patients. J Clin Periodontol. 2009;36(12):1004-10.
• Inflammatory mediators, such as TNF-a, and levels of P gingivalis are known to
aggravate or partially cause the disease
Kaur S., White S., Bartold P.M. Periodontal disease and rheumatoid arthritis: a systematic review. J
Dent Res. 2013;92(5):399-408
• The presence of periodontitis is also shown to hamper RA treatment with TNF-a
blockers
Savioli C, Ribeiro AC, Fabri GM, et al. Persistent periodontal disease hampers anti-tumor necrosis
factor treatment response in rheumatoid arthritis. J Clin Rheumatol 2012;18(4):180–4
53. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Rheumatoid arthritis
• Periodontal treatment may ameliorate the clinical manifestations of RA
• Periodontal treatment leading to improvement in biochemical markers in persons
suffering from RA.
• Improvement in signs and symptoms of RA occurred, regardless of whether the RA
patients were under anti-TNF-a treatment
• Anti-TNF-a RA treatment had no effect on the periodontal health without
periodontal therapy.
54. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Rheumatoid arthritis - AP
• Patients with RA can be more prone to develop AP(Karatas et al, 2020)
55. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Other diseases
• Chronic kidney disease
• Metabolic syndrome
• Obesity
• Inflammatory bowel diseases
• Cancer
• Alzheimer disease/cognitive function decline
56. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Alzheimer disease
• Alzheimer’s disease (AD) is an irreversible, progressive chronic neurodegenerative
dementing disease
• AD is associated with neuronal degeneration and atrophy in the brain leading to
death. In a normal non-AD diagnosed brain, amyloid-β (Aβ) proteins are found in-
and-around the neurons.
• The apolipoprotein E gene (APOE) (particularly the E4 allele) is the strongest genetic
risk factor for late-onset Alzheimer disease.
• APOE is implicated in the metabolism, aggregation and deposition of amyloid-β
• P. gingivalis gingipains cleave APOE at Arg residues, suggesting an additional
possible mechanism whereby P. gingivalis might contribute to Alzheimer disease.
• P. gingivalis can cause neuroinflammation also in the absence of APOE
57. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Inflammatory bowel diseases
• Potential patomechanisms
• Oral pathogens – ingestion – induction of MF
(inflammatory process): IL-1β secretion
• Oral MO’s – Th17 cells – lymphocyta trafficing to the
gut and binding to the DC – Resident oral pathogens
activate via DC and IL-1β secretion of MF
ectopically colonized oral pathobionts may
exacerbate colitis by activating both
• innate immunity (local inflammatory macrophages)
and
• adaptive immunity (transmigrated TH17 cells of oral
origin)
Ábra: Hajishengallis G and Chavakis T:
Local and systemic mechanisms linking periodontal disease and
inflammatory comorbidities
Nat Rev Immunol. 2021 Jan 28:1-15
58. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Inflammatory bowel diseases
• Periodontitis is a potential etiologic factor by:
• dysbiosis
• damage of the epithelial barrier function (tight-junction, etc.)
• Increased pro-inlammatory citokin expression – local inflammatory process
• Induction and enhancement of Th1 mediated immun response
• Potential periodontopathogens
• (P. gingivalis, F. nucleatum, P. intermedia, Klebsiella spp., Enterobacter spp., etc.)
59. Department of Oral Diagnostics
Peter Valyi DMD, PhD
Associate professor
Colorectal cancer
• The gut microbiota of patients with colorectal cancer exhibits increased species richness and
abundance (compared with healthy controls), and this is attributed in part to ectopic
colonization and expansion of bacteria deriving from the oral cavity
(i.e. F. nucleatum, Parvimonas micra, Peptostreptococcus stomatis, Solobacterium moorei and
Porphyromonas asaccharolytica)
• F. nucleatum can promote the growth and migration of human CRC cells and their resistance to
chemotherapy, as well as enhance intestinal tumorigenesis
• Oral F. nucleatum can haematogenously reach the colon, where it exhibits tropism for CRCidentical
strains of this organism are detected in the saliva and colorectal tumours of patients with CRC
• CRC cells overexpress a carbohydrate moiety that is bound by the F. nucleatum lectin, which also
induces the release of prometastatic chemokines
• Another F. nucleatum adhesin stimulates the growth of CRC (but not of non-cancerous) cells
• F. nucleatum alters the tumour microenvironment in a manner that facilitates CRC progression;
specifically, it recruits tumour-infiltrating myeloid-derived suppressor cells
• Besides F. nucleatum, several other oral bacteria are suspected to play a role in different types of
carcinoma
Cardiovascular diseases are the leading cause of mortality in the western world. The relationship between periodontitis and cardiovascular diseases (CVD) has been verified widely