Abstract
Orofacial granulomatosis (OFG) is a rare disfiguring disease of unknown aetiology. It is characterised by deep seated granulomatous inflammation in the oral cavity which may also affect the lips and perioral region. The precise pathogenesis remains unknown but previous studies have demonstrated links with dietary sensitivity, allergy and Crohn’s disease (CD). It has been suggested that an alteration in the oral microbiome could play a role in the disease. Clinically, OFG remains challenging to diagnose and treat, with a lack of objective biochemical markers for disease assessment and monitoring. The use of probiotics as treatment for OFG is an attractive option and has not been studied in great detail. Thus, the aims of this thesis were to:1. Characterise the oral microbiome in OFG in an attempt to further illuminate the underlying pathogenesis of the disease.
2. Evaluate the salivary calprotectin assay for use as an oral diagnostic biomarker in OFG and CD.
3. Evaluate the use of a novel probiotic Lactobacillus brevis (CD2) in the treatment of active OFG.
Microbiome analysis was performed using 16S rRNA gene analysis and revealed no differences in diversity or richness in salivary bacterial communities. However, there was a relative abundance of Streptococcus salivarius in OFG and CD patients as compared with controls.
Salivary calprotectin analysis using Enzyme-Linked ImmunoSorbent Assay (ELISA) was carried out over a two year period in 252 subjects. Salivary calprotectin levels were found to be significantly higher in OFG patients with concurrent CD, and patients with intra-oral involvement compared with controls. There was poor correlation with the Oral Disease Activity Score (ODAS) indicating salivary calprotectin levels to be a poor marker of OFG disease activity but could indicate the presence of concurrent gut CD.
The effect of CD2 Lactobacillus brevis lozenges were studied in 28 patients with OFG. These were well tolerated and were found to modestly reduce median ODAS but with a greater reduction in oral soreness.
The evidence presented in this thesis suggests that changes in the microbiome may be involved in the pathogenesis of OFG and CD.
Salivary calprotectin appears to be of limited value as a marker of disease activity, however, there would be benefit from the identification and development of a biomarker of disease presence and activity. Streptococcus salivarius could be a potential biomarker for OFG and CD. Potential modulation of the microbiome with probiotic treatment appears to be well tolerated and beneficial.
| Date of Award | 1 Aug 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Jeremy D. Sanderson (Supervisor) & Michael Escudier (Supervisor) |