Impacto da doença cárie no perfil metabolômico salivar de pacientes com encefalopatia crônica não progressiva

Resumo (EN)

Introduction: Chronic Non-Progressive Encephalopathy (CNPE) is a neurological condition that can alter physiological processes, including the oral environment. Dental caries is a multifactorial disease whose development can be influenced by systemic and local factors, such as the salivary profile. Metabolomics has emerged as a promising tool for identifying biomarkers that reflect these biochemical changes. Objective: To investigate the impact of dental caries on the salivary metabolomic profile of individuals with and without CNPE, aiming to identify characteristic biochemical signatures associated with the neurological condition and caries activity. Methods: This was an observational, cross-sectional, and analytical study with a convenience sample of 60 individuals divided into four groups (n=15 each): G1 (CNPE without caries), G2 (CNPE with caries), G3 (without CNPE and without caries), and G4 (without CNPE with caries). Unstimulated saliva was collected in the morning, following a two-hour fasting period, and stored at -80 °C until analysis. Caries was assessed using the DMFT/dmft index. Metabolomic analysis was conducted via gas chromatography-mass spectrometry (GC-MS) at the DEMPSTER Mass Lab of the Polytechnic School of the University of São Paulo. Statistical analysis was performed using Kruskal-Wallis and Chi-Square (χ²) tests. Results: Distinct metabolomic signatures were observed across the groups. G1 showed elevated levels of 2,6-Dimethylmorpholine-4-carbothioic acid, D-glucopyranose derivatives, maltose, urea, glutamic acid, and L-proline (p<0.0001), consistent with a soft diet, limited mastication, and metabolic adaptation to CNPE. G2 presented increased nitrogen-containing metabolites (N,O-Bis(trimethylsilyl)-L-phenylalanine, leucine di-TMS, lysine) and fermentative compounds (acetic acid, 2,3-butanediol diTMS) (p<0.0001), suggesting a synergistic interaction between the neurological condition and caries activity. G3 showed a profile compatible with healthy saliva, including stable levels of phenol, 4-methyl-, L-glutamine, glycine N-benzoyl-, and 1H-indole-3-acetamide (p<0.0001), indicating salivary homeostasis and absence of active inflammation. G4 revealed a more complex profile associated with intense caries activity, characterized by metabolites linked to bacterial degradation and oxidative stress, such as phenol, 4-[(dimethylamino)methyl]-3,5-dimethyl-, mequinol, glycine N-benzoyl-, and 8-hydroxy-2,2-dimethyl-8-phenyl-oct-5-en-3-one (p<0.0001). Conclusion: Both CNPE and dental caries significantly influence the salivary metabolomic profile, activating distinct metabolic pathways and resulting in specific biochemical signatures. Some metabolites, such as urea, glycine N-benzoyl-, and phenolic derivatives, were shared across groups, indicating their potential as salivary biomarkers. These findings highlight the value of salivary metabolomics as a complementary tool for screening and monitoring caries, particularly in populations with special healthcare needs.