Date of Completion

8-24-2015

Embargo Period

8-24-2015

Keywords

fungi, oral mycobiome, next generation sequencing, oral mucositis, health, candidiasis, Malassezia, Candida

Major Advisor

Linda Strausbaugh

Associate Advisor

Rachel O'Neill

Associate Advisor

Patricia Diaz

Associate Advisor

Michael O'Neill

Associate Advisor

Anna Dongari-Bagtzoglou

Field of Study

Genetics and Genomics

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Fungal Communities in Oral Health and Disease

Amanda K. Dupuy, PhD

University of Connecticut, [2015]

With advances in, and cost reduction of next generation sequencing technologies, assessing the presence of microbes in host niches in healthy and diseased states has become a more feasible task. However, these studies are often only limited to bacterial characterization, ignoring other important community members such as fungi, viruses, and protists. The research presented here begins to fill this gap by creating a roadmap for fungal community analysis. With fungal outbreaks on the rise, it is essential that the fungal kingdom is included in future microbiome analyses to gain a more comprehensive understanding of commensal species, how they maintain a healthy niche, and their impact on acquired diseases.

One particularly at-risk group of immune compromised patients are those undergoing chemotherapy. Approximately 40% of such patients develop a debilitating side effect known as oral mucositis, which is complicated by severe pain, inability to eat and speak, and severe bacterial and fungal infections. The research in this dissertation focuses on three aims necessary for answering the question of how fungal genera are implicated in oral mucositis. First, we present a roadmap from sample processing to data analysis, describing challenges and solutions for characterizing fungal communities in any human-health related metagenomics study. Second, we address the healthy fungal mycobiome of saliva, providing evidence for new and existing members of the oral niche, while assessing the temporal variability in community composition in a healthy state. Third, we characterize the oral genera during chemotherapy in a longitudinal study of cancer patients, and document their changes during the progression and development of oral mucositis. Revealing and meeting the challenges associated with fungal metagenomic analysis by means of initial hand curation will pave way for development of new, much needed library preparation and bioinformatics tools. But above all, pinpointing community trends for susceptible subjects will ultimately provide unprecedented insight for implementation of prophylactic measures in cancer patients.

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