Date of Award
Doctor of Philosophy (PhD)
Early childhood caries (ECC) is one of the most common chronic diseases worldwide and remains a serious public health crisis in developing countries and socioeconomically disadvantaged communities. Caries is a complex polymicrobial, sugar-driven disease caused by interactions between the biofilm and tooth surface. While there is a general understanding of the microbial processes driving dental caries development and progression, the microbiota associated with the initiation and progression of dental caries have yet to be fully characterized. The most-studied species associated with tooth health and disease are the oral streptococci. Nevertheless, there are still large gaps in our knowledge of the complex roles that the oral streptococci play within the plaque biofilm. In addition to bacteria, fungi are also known to be commensal organisms living in the oral cavity. However, the oral fungal mycobiome associated with caries is not well characterized and its role in disease is unclear.
HIV infection leads to severe suppression of the human immune system which leads to increased risk of developing opportunistic infections. Many of these infections occur in the oral cavity and there is strong evidence to suggest that the human oral microbiome and HIV are closely linked. Recent studies have found that HIV-infected children are at an increased risk of caries development when compared to their uninfected peers. However few studies have examined the oral microbiome community associated with both HIV infection and caries development.
Herein, this study examined multiple aspects of the oral microbiome associated with dental caries disease progression. Firstly, to gain a higher taxonomic resolution of the oral streptococci I developed a novel gene locus, 30S-S11 rDNA, for high-throughput amplicon sequencing. Results from this study showed improved taxonomic resolution of the oral streptococci when compared to the 16S-rRNA V4 hypervariable region. Moreover, the results revealed different amplicon sequence variants (ASVs) within a species changed in abundance at different stages of caries progression. These findings suggest that strains of a single species may perform distinct role along a biochemical spectrum associated with health and disease.
Next, I examined the oral fungal mycobiome associated with caries initiation and progression using site-specific sampling. These results identified 139 fungal species with Candida albicans and Candida dubliniensis being the most abundant species. Significant differences in the community composition were observed when comparing completely healthy teeth and severely diseased teeth. Interestingly, C. dubliniensis increased steadily as caries progressed, suggesting that C. dubliniensis may play an important role in caries pathogenicity. In contrast, four health-associated fungal taxa have the potential to antagonize the cariogen S. mutans via xylitol production, suggesting a possible fungal mechanism that could contribute to maintenance of dental health.
Lastly, the oral mycobiome in supragingival plaque samples from HIV-infected (HI), HIV-exposed but uninfected (HEU), and HIV-unexposed and uninfected (HUU) children with and without caries was examined. I found that HIV infection and exposure resulted in changes to the supragingival plaque mycobiome between health and caries. Overall, a reduction in community diversity as caries disease progressed was observed. Regarding HIV status, HI children had the lowest diversity and HEU children have the highest diversity. Candida albicans was the most abundant species identified, with 177 different ASVs. Interestingly, the most abundant C. albicans ASV was different in HEU children than in HI and HUU children. HEU children also had the lowest abundance of C. albicans and the highest number of health-associated taxa. Contrastingly, HI and HUU children had the highest abundance of C. albicans and more disease-associated taxa. These data show that HEU children harbor a fungal mycobiome enriched in taxa most often found associated with tooth health when compared to HUU and HI children.
O'Connell, Lauren, "Dynamics of the Supragingival Dental Plaque Microbiome and Its Implications in Early Childhood Caries (ECC)" (2022). All Dissertations. 3040.
Supplemental_Table2_SampleMetadata.xlsx (12 kB)
Supplemental_Table3_RarefiedOTUTable.xlsx (56 kB)
Supplemental_Table4_DESeq2Results_fulldataset.xlsx (238 kB)
Supplemental_Table5_MockCommStrainsUsed.xlsx (9 kB)
Additional File S1.xlsx (11 kB)
Additional File S2.xlsx (32 kB)
Additional File S3.xlsx (278 kB)
Additional File S7.xlsx (14 kB)
Table_S1_SummaryofDemographicsTestedforCommunityComparisons.xlsx (9 kB)
Table_S2_SampleMetadata.xlsx (16 kB)
Table_S3_RarefiedCountTable.xlsx (148 kB)
Table_S4_DESeqResults_Combined.xlsx (1451 kB)
Available for download on Tuesday, March 21, 2023