Urine metabolomics of women from small villages exposed to high environmental cadmium levels.

The present study aimed to identify urine metabolites in women exposed to high cadmium (Cd) levels. Twenty-one women exposed to environmental Cd and 12 age-matched controls were categorized as high exposure (urine Cd ≥ 15 μg/g creatinine; n = 9) or low exposure (15 μg/g creatinine > urine Cd > 5 μg/g creatinine; n = 12). Low-molecular weight metabolites in urine were analyzed by gas chromatography and mass spectrometry after derivatization. An orthogonal partial least-squares discriminant analysis model was constructed, and metabolites from the dimensional model were selected according to the variable importance in projection (>1). Metabolites differing significantly in abundance between different exposure groups were identified by searching mass spectral databases, and related pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes. Approximately 110 significantly different metabolites were detected with variable importance in projection > 1, and 48 of them were found to differ markedly in abundance among the 3 groups. Twenty-seven matched with known metabolites, including 22 significantly increased and 5 markedly decreased in the high-exposure group (p < 0.01). Kyoto Encyclopedia of Genes and Genomes results indicated that carbohydrate, amino acid, bone, and intestinal flora metabolism and the tricarboxylic acid cycle were affected by Cd exposure. The present study identified metabolites that differed in abundance in response to Cd exposure. Further studies may connect these biomarkers to early damage caused by Cd.