Alcheva, Aleksandra2024-01-052024-01-052023-09https://hdl.handle.net/11299/259702University of Minnesota Ph.D. dissertation. September 2023. Major: Environmental Health. Advisor: Irina Stepanov. 1 computer file (PDF); vii, 113 pages.Chemicals present in tobacco smoke and e-cigarettes may cause unique alterations to an individual’s oral microbiome (microorganisms that reside in the oral cavity), which in turn is likely to have an impact on immune responses, inflammatory processes, uptake and metabolism of tobacco toxicants and carcinogens and the overall health status. This dissertation involves three complementary studies which cumulatively provide important insights into the utility of the oral microbiome as a comprehensive and robust biological matrix for studies of tobacco product use and disease susceptibility. The first study investigated the responsiveness of the oral microbiome to changes in tobacco exposure through an 8-week trial in which persons who smoke were asked to switch to e-cigarette use. Compared to baseline smoking, notable changes in the oral microbial composition were found in those study participants who switched to exclusive use of e-cigarettes. These findings suggest that the oral microbiome could potentially serve as an indicator of changes in smoking-derived exposures and potentially for verification of e-cigarette use status in observational and interventional studies. The second study aimed to determine whether the oral microbiome is associated with the tobacco-induced biological effects in the oral cells of individuals who smoke. In this study, specific taxa of the oral microbiome in persons who smoke were associated with high levels of HPB-releasing DNA adducts (DNA damage caused by tobacco-specific carcinogens) in their oral cells. Many of these taxa contribute to nitrate metabolism and subsequently to carcinogenic nitrosamine formation in oral cavity – a potential mechanism through which the oral microbiome may be related to oral cell DNA damage and/or contributes to tobacco-related cancer risk. The findings of this study suggest that the oral microbiome can serve as a predictor of tobacco-induced DNA damage in oral cavity, and therefore used as a tool for evaluating tobacco product harm and/or as a marker for assessing cancer susceptibility of individuals who smoke. The third study explored the potential effect of sociodemographic factors on the oral microbiome of individuals who smoke. Answering this question helps to inform future studies that may use the oral microbiome as a matrix for assessing tobacco-derived exposures and biological effects. In this study, self-identified race emerged as a significant factor associated with the oral microbial composition. Given that race is a social construct, this finding likely reflects the cumulative effects of social and environmental stressors on the oral microbiome. Future studies of the oral microbiome as a biomarker of tobacco-derived exposures and biological effects should adjust for such stressors. In addition, this finding suggests that the oral microbiome could be used as a tool in studies exploring factors contributing to health inequities. In conclusion, this comprehensive investigation advances our understanding of the interplay between tobacco exposure, the oral microbiome, and biological effects. It positions the oral microbiome as a promising marker for tobacco regulatory research and in studies of disease susceptibility and prevention.enexposure and effectsoral microbiometobacco productsThesis or Dissertation