Dean, David RGem, Hakan2024-09-092024-09-092024Gem_washington_0250O_26511.pdfhttps://hdl.handle.net/1773/51890Thesis (Master's)--University of Washington, 2024Oral mucositis is a significant and debilitating complication of allogeneic hematopoietic stem cell transplantation. Though the pathophysiology of oral mucositis has been studied extensively, the precise mechanisms remain incompletely characterized, particularly in relation to the influence of the oral microbiota. The oral microbiota is recognized as one of the most diverse and complex microbial communities in the body, and understanding its impact on the development and severity of oral mucositis may improve patient outcomes. A prospective, non-interventional, single center study was conducted with longitudinal sampling of four distinct microbial communities in the oral cavity (saliva, gingival crevicular fluid, supragingival plaque, and subgingival plaque) in patients receiving allogeneic hematopoietic stem cell transplantation at four timepoints (baseline, days +14, +28, and +84 post-transplant). Calibrated examiners scored oral mucositis severity using a validated instrument, the Oral Mucositis Assessment Scale, at days +7, +14, +21, +28, and +84. Shotgun metagenomic sequencing was used to characterize the oral microbiota. Microbial composition and mucositis scores were compared to examine potential microbial associations with mucositis severity. Three species of salivary bacteria at baseline (Capnocytophaga sputigena, Prevotella nigrescens, and an Olsenella species) were significantly enriched in patients with high mucositis scores at day +7, and three species of supragingival plaque bacteria at day +14 (Capnocytophaga sputigena, Prevotella nigrescens, and a Granulicatella species) were significantly enriched in patients with high mucositis scores at day +14. Age, sex, and conditioning intensity were identified as non-microbial factors correlated with mucositis severity at specific timepoints. Oral microbial diversity in saliva and supragingival plaque declined from baseline to day +14 but recovered in saliva by day +28 and in supragingival plaque by day +84. Results suggest that microbial factors may influence mucositis severity in patients receiving allogeneic hematopoietic stem cell transplantation. Further characterization of microbial dynamics is essential for future hypothesis-driven research to investigate the potential role of antibiotic and/or probiotic interventions in the prevention and management of oral mucositis.application/pdfen-USCC BYallogeneic hematopoietic stem cell transplantationoral microbiomeoral microbiotaoral mucositisDentistryOncologyMicrobiologyDentistryThesis