The impact of Candida albicans phenotype on the oral microbiome

Butcher, Mark Craig (2025) The impact of Candida albicans phenotype on the oral microbiome. PhD thesis, University of Glasgow.

Abstract

Candida albicans is a prolific opportunistic pathogen and resides within the mucosa associated microbiome in the human body. The presence of Candida albicans has commonly been reported as a potential indicator or risk factor in the development of caries in children and adults. Typically commensal in nature, it has also been well established that the development of pathogenicity in Candida albicans is driven by environmental factors which lead to its overabundance or phenotypic switching to a more pathogenic hyphal morphology. While this has been found to aid in adhesion to oral surfaces, both biological and inert, it also provides a substrate and environmental niche for other micro-organisms. In this study, we propose that alteration of Candida phenotype directly influences the microbial and cariogenic profile of a fixed model biofilms and complex, undefined biofilms.

Firstly, by employing a meta-analytic approach to examining relevant media related to the oral microbiome to synthesise findings which examine the influence of bacteria within the microbiome and the ability to predict onset or development of caries based on these findings. Following this, C albicans isolates with high and low biofilm phenotype were selected for co aggregation assessment with other organisms of a previously published “caries” biofilm model and profiled based on biomass, metabolism, drug response and response to environmental stimuli such as sucrose. Saliva was pooled from 19 individuals and used as starter biofilm culture for ex-vivo experiments ex-vivo models were grown on bovine enamel and assessed for shifting microbial profile, acidogenesis and alteration of substrate when exposed to environmental stimuli. Additionally, Complex bacterial biofilms ± Candida albicans were formed over 5 days ± fluconazole (FLU) or amphotericin B (AMB), with biofilms sampled every 24 h for 120 hrs. DNA was extracted with propidium monoazide to amplify live cell DNA. Microbiome analysis was performed using long read Nanopore sequencing.

Analysis of the literature containing 16S rRNA sequencing data relating to caries revealed insights into the collection, curation, and storage of sequencing data which highlighted a lack of standardisation in the field. In addition, though some significance was found between studies, it was determined that more data would be required to be able to reliably use microbiome data as a predictive tool for caries pathology. When screening isolates, C albicans was found to buffer pH profile of “caries” organisms in both dual and multi-species formats. Using sucrose as an environmental stimulus of multi-species biofilms resulted in both a shift in microbial distribution and a higher erosion profile in bovine enamel. Additionally, Candida was shown to influence the distribution of organism taxonomy in a complex saliva-derived ex-vivo model where it was also identified that environmental conditions such as media requirements, substrate development and challenge through oral hygiene regimen or antifungal exposure can also impact the oral microbiome. Overall, Candida was shown to provide a key role in the oral in-vitro microenvironment, in the context of caries, and in a strain-dependent manner, using in-vitro and ex-vivo methods. This has implications in both the application of strains of C. albicans in fixed models for testing of novel compounds and in applications of personalised healthcare where the ramifications of affecting these core organisms, via antimicrobial interventions, could have further, unexpected effects.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology; R Medicine > RK Dentistry
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Funder's Name: Biotechnology and Biological Sciences Research Council (BBSRC)
• Supervisor's Name: Brown, Dr. Jason and Combet-Aspray, Professor Emilie
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85401
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 20 Aug 2025 09:47
• Last Modified: 20 Aug 2025 09:49
• Thesis DOI: 10.5525/gla.thesis.85401
• URI: https://theses.gla.ac.uk/id/eprint/85401

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