Abstract
Electronic cigarettes (e-cigs) have become increasingly popular, particularly among younger populations. This study aimed to evaluate the salivary proteome of e-cig users and identify potential alterations in saliva composition. Participants were divided into the Electronic Cigarette Group (EG, n = 25 regular exclusive users) and the Control Group (CG, n = 25 nonsmokers/nonusers), matched by sex and age. Clinical examination and unstimulated saliva collection were performed for proteomic analysis. A total of 1,773 proteins were identified, of which 92 had consistent quantitative values between groups. Comparison using the Wilcoxon-Mann-Whitney test revealed 22 proteins with differential abundance (p ≤ 0.05), most of them up-regulated in EG, notably Peroxiredoxin-1, while few showed decreased abundance. Functional enrichment analysis highlighted pathways related to keratinization, keratinocyte differentiation, and stress response, suggesting activation of cellular defense and adaptation mechanisms. These results indicate that e-cig aerosol exposure induces biological alterations in the oral environment, including modulation of proteins linked to oxidative stress and epithelial integrity. Overall, the findings emphasize the need for long-term monitoring of e-cig users and reinforce the importance of educational strategies to counter the perception of low risk associated with electronic cigarettes.