Salivary Metabolomic Signatures and Body Mass Index in Italian Adolescents: A Pilot Study

Abstract

Context Obesity surveillance is scarce in adolescents and little is known on whether salivary metabolomics data, emerging minimally invasive biomarkers, can characterize metabolic patterns associated with overweight or obesity in adolescents. Objective This pilot study aims to identify the salivary molecular signatures associated with body mass index (BMI) in Italian adolescents. Methods Saliva samples and BMI were collected in a subset of n=74 young adolescents enrolled in the Public Health Impact of Metal Exposure (PHIME) study (2007-2014). A total of 217 untargeted metabolites were identified using LC-HRMS. Robust linear regression was used to cross-sectionally determine associations between metabolomic signatures and sex-specific BMI-for-age z-scores (z-BMI). Results Nearly 35% of the adolescents (median age: 12 years; 51% females) were either obese or overweight. A higher z-BMI was observed in males compared to females (p=0.02). One nucleoside (deoxyadenosine) and two lipids (18:0-18:2 phosphatidylcholine and dipalmitoyl-phosphoethanolamine) were negatively related to z-BMI (p<0.05), whereas two benzenoids (3-hydroxyanthranilic acid and a phthalate metabolite) were positively associated with z-BMI (p<0.05). In males, several metabolites including deoxyadenosine, as well as deoxycarnitine, hyodeoxycholic acid, N-methylglutamic acid, bisphenol P, and trigonelline were downregulated, while three metabolites (3-hydroxyanthranilic acid, theobromine/theophylline/paraxanthine, and alanine) were upregulated in relation to z-BMI (p<0.05). In females, deoxyadenosine and dipalmitoyl-phosphoethanolamine were negatively associated with z-BMI while deoxycarnitine and a phthalate metabolite were positively associated (p<0.05). A single energy-related pathway was enriched in the identified associations in females (carnitine synthesis, p=0.04). Conclusion Salivary metabolites involved in nucleotide, lipid, and energy metabolism were primarily altered in relation to BMI in adolescents.