LAUSR

Use of electronic nicotine delivery systems (ENDS) is becoming increasingly prevalent. ENDS aerosols contain a variety of toxic components that may adversely impact health. Although exposure to traditional cigarette smoke is a risk factor for periodontal disease, the effects of ENDS on oral health have not been adequately examined. To evaluate potential oral health effects associated with ENDS use, a pilot study was performed with 14 current ENDS users and 16 never tobacco users. Participants completed questionnaires about their ENDS use and overall health. Saliva samples were assessed for differential biomarkers of inflammation, toxicity, and disease development. This included evaluation of specific inflammatory cytokines and the global assessment of alterations in metabolites. ENDS users were determined to have elevated saliva levels of interleukin-1β and tumor necrosis factor-α indicative of inflammation. Metabolite profiling determined 368 metabolites were differentially expressed in the saliva of ENDS users versus never tobacco users. Cotinine, the primary metabolite of nicotine, was the most significantly altered metabolite between the groups. Increased levels of prostaglandins and leukotrienes indicated that ENDS users exhibited increased arachidonic acid metabolism compared to never tobacco users. Additionally, a variety of other metabolites known to be involved in immune signaling such as gangliosides, ceramides, angiotensin, and others were also different between groups. Overall, our pilot study demonstrates differential saliva component profiles in current ENDS users, which may contribute to periodontal disease development. These alterations suggest specific pathways of oral disease induced by ENDS use and could be utilized as potential future biomarkers. Impact statement The use of traditional tobacco products is a known risk factor for the development of diseases including periodontal disease. To date, the potential oral health effects related to electronic nicotine delivery systems (ENDS) use is unknown. This study collected saliva from ENDS users and never tobacco users to examine differences in the oral cavity of inflammatory cytokines and metabolites. The identification and measurement of these ENDS-related changes provide insight into disease pathways potentially associated with ENDS use. The utilization of saliva samples collected from human participates enhances the application of the findings compared to the majority of studies using cell culture and animal models. In addition, these foundational findings can inform future studies to examining specific pathways identified, interventional approaches, and application of translatable biomarkers of ENDS use.