Student thesis: Doctoral ThesisDoctor of Philosophy



The microbiota of apical periodontitis (AP) is extremely diverse. During root canal treatment, the gloves worn by dentists were found to be heavily contaminated with nosocomial pathogens transferred from the patients’ saliva or skin, affecting the clinical outcome. Furthermore, it has been found that bacteraemia occurs following root canal treatment. Therefore, root canal infection and its treatment can be an enfolded primary infective focus for the dissemination of microbes via periapical vasculature, and their subsequent seeding in another organ. Apart from driving transient bacteraemia, oral-systemic interactions and their consequent outcomes could also be due to chronic systemic inflammation because of circulating active inflammatory markers. Studies have suggested a relationship between chronic AP and the risk of developing cardiovascular diseases (CVDs). Therefore, the challenge is to find that confirmatory link between contaminated gloves, nosocomial endodontic infections, and adverse systemic conditions.


The aims of this longitudinal study are to:
• Assess the effect of apical periodontitis on serum and salivary levels of inflammatory markers.
• Assess the effect of root canal retreatment and periapical surgery on the levels of inflammatory markers at 3-, 6-, and 12-months post-treatment.
• Correlate the levels of inflammatory markers with the pre-operative size of the radiolucency, treatment outcome, and levels of metabolic syndrome factors.
• Characterise salivary, gloves, endodontic microbiota, and bacteraemia profile and investigate any association between nosocomial endodontic infections and bacteraemia.

Materials and methods

115 participants were recruited (65 with AP, 50 controls). Saliva, gloves, blood, and intracanal samples were collected from recruited patients while blood and saliva samples were collected from healthy controls. Patients were reviewed after 3-, 6-, and 12-months following treatment. Serum and saliva samples were analysed using Multiplex microbead immunoassay and ELISA for identifying the levels of interleukin (IL) - 1b, IL-6, IL-8, tumor necrosis factor (TNF) -a, matrix metalloprotease (MMP) -2, MMP-8, MMP-9, high sensitive C-reactive protein (hs-CRP), fibroblast growth factor (FGF)-23, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, E-selectin, pentraxin 3, asymmetric dimethylarginine (ADMA), and complement (C3) and comparing these levels with those of healthy controls. Markers were further analysed at review appointments and correlated with metabolic syndrome factors, as well as with the size of radiolucencies and treatment outcome. Bacterial DNA extraction was undertaken from collected samples, and highthroughput sequencing of the 16S rRNA gene (V1-V2 hypervariable region) was performed using the Illumina MiSeq 300 platform according to manufacturers’ protocol.


The presence of AP was seen to have caused an increase in the serum levels of IL-1b, hs-CRP, FGF-23, and ADMA and salivary hs-CRP at baseline. However, the successful treatment of AP resulted in reduction on the levels of FGF-23, pentraxin 3, TNF-a, ADMA, and VCAM-1, hence reducing the systemic burden of AP. Furthermore, the most abundant ASV from intracanal samples including Prevotella, Streptococcus, Staphylococcus and Actinomyces were also recovered from pre-operative blood samples, indicating bacteraemia associated with root canal infections. Finally, the nosocomial endodontic pathogens, Staphylococcus and Cutibacterium, were abundant in gloves, intracanal and blood samples.


1. AP increased the levels of inflammatory markers before the treatment.
2. Successful root canal treatment helps in reducing the levels of inflammatory markers.
3. The microbiome of saliva, blood, gloves, and intracanal are diverse, however, common
microbial taxa were identified between these different sources.
4. Nosocomial pathogens were identified from gloves and inside the canal before
obturation and in post-operative blood samples, suggesting bacteraemia.
5. AP and root canal treatment can cause bacteraemia

Date of Award1 Jun 2022
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorDave Moyes (Supervisor), Francesco Mannocci (Supervisor) & Sadia Niazi (Supervisor)

Cite this