Investigation of the Molecular Differences in Metabolomic and Proteomic Profiles Between Smokers and Nonsmokers

Abstract Introduction Tobacco exposure has been associated with molecular alterations in the oral cavity, including changes related to inflammation and oxidative stress. This study aimed to characterize metabolomic and proteomic differences between young smokers and nonsmokers using a non-invasive buccal swab-based multi-omics approach. Methods Using a cross-sectional study design, we performed semi-quantitative metabolomic and proteomic profiling via liquid chromatography–mass spectrometry (LC–MS). We analyzed buccal swabs from a cohort of 108 young adults (18–25 years) to investigate smoking-associated molecular changes with putative identification of compounds. Results Smokers displayed increased levels of eight metabolites ( N -acetylcadaverine, N -acetylspermine, pipecolic acid, tyramine, methylthiophene, spermidine, 5-oxoproline, and histidine). Proteomic profiling identified thirteen significantly elevated proteins in smokers including, C-X-C motif chemokine ligand 10 (CXCL10), C-reactive protein (CRP), salivary alpha-amylase (AA), neutrophil gelatinase-associated lipocalin (NGAL), transferrin, macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), serum amyloid A (SAA), endothelial PAS domain protein 1 (EPAS1), myeloid-related protein 8 (MRP8/S100A8), myeloid-related protein 14 (MRP14/S100A9), immunoglobulin A (IgA), and haptoglobin (all p < 0.05). These findings indicate a distinct molecular profile in smokers characterized by inflammatory and oxidative-stress-associated alterations in the oral cavity. Our findings are broadly consistent with previous reports and extend current evidence on smoking-associated metabolomic and proteomic differences in young adults. Conclusions This study suggests that buccal swab multi-omics may help characterize smoking-associated molecular alterations in young adults and highlights several inflammatory-related molecules as targets for future validation. Further studies are needed to validate these findings and clarify their biological and potential clinical relevance.