Identification of salivary and plasma biomarkers for obesity in children by non-targeted metabolomic analysis

Abstract

Chemical compounds in the saliva most likely to be associated with obesity are identified in a metabolomic analysis of paired whole saliva and plasma samples from 68 children (10-year old) who have also been evaluated for their gingival redness.\n\nResultsThrough metabolomic analysis119 compounds were found only in saliva, 210 only in plasma and 126 in both. The most common plasma metabolites were lipids. The most common saliva metabolites were peptides. Amino acids and their metabolites were common in both samples.\n\nSurrogate indicators were identified by computing correlations between saliva and plasma. 29 of the 126 found in both saliva and plasma had significant positive correlation and only 4 of those (urate, creatinine, pipecolate and hydroxyproline) were associated with obesity as potential surrogate biomarkers. The uremic toxin N1-Methyl-2-pyridone-5-carboxamide (2PY) was also elevated in the saliva of obese children. 21 biochemicals were elevated in both obesity and gingivitis suggesting that some biochemical pathways for gingivitis and obesity are shared.\n\nOf the metabolites found only in saliva, 35 were associated with obesity (p<0.01). The most significant was phosphate. Saliva had 53 dipeptides, seven of which were associated with obesity. Two volatile amines (putrescine and cadaverine) and their amino acid precursors (ornithine and lysine) were also associated with obesity.\n\nOf the metabolites found only in plasma, 64 were associated with obesity (p<0.01). Significant increases in branched-chain and aromatic amino acids, significant reductions in serotonin, serine, and glycine and increased androgen metabolism are changes observed in 10-year old obese children that have also been reported with adult patients having type II diabetes.\n\nConclusionsSalivary urate may be a valuable measure of metabolic disease particularly in association with fructose consumption. Elevated salivary creatinine levels and presence of 2PY suggests a possible association of obesity with developing kidney disease in obese children. Though not a surrogate variable, salivary phosphate, (AUROC= 0.8) could also be an important indicator of obesity. Cadaverine, putrescine and dipeptides are also likely oral bacterial products that could help define the metabolic pathways responsible for obesity. The results of this study indicate that salivary metabolites can be important indicators of developing metabolic disease in children and provide a biochemical signature in the pathways that lead to obesity.