Identification of urine biomarkers associated with early puberty in children: An untargeted metabolomics analysis

Abstract

A trend toward earlier pubertal maturation in both sexes has been shown in many countries. Early puberty affects an increasing proportion of children for reasons that remain obscure. Novel candidate biomarkers are strongly needed. We sought to apply untargeted metabolomic profiling to identify triggering mechanisms and candidate biomarkers in children with early puberty. Participants aged 7 – 12 years old were recruited directly from two elementary schools of Bengbu, Anhui Province, China, from Feb 2021 to May 2021. Early puberty was determined by breast and testicular development at baseline (May 2021) and 6-month later. Ultra-high-performance liquid chromatography-based untargeted metabolomic profiling was performed on urine samples of children with early puberty and control subjects. Metabolomic profiling for early puberty in a sex dependent manner. For boys, we identified several perturbed pathways, including histidine metabolism, glycine, serine and threonine metabolism, and selenoamino acid metabolism, associated with early puberty. In contrast, there were differences in pyruvate metabolism, one carbon pool by folate, and D-glutamine and D-glutamate metabolism pathways in girls with early puberty compared with controls. In addition, 4-hydroxyhippuric acid and 5-methoxytryptophol were shown as potential independent diagnostic biomarker for early puberty in boys, 3-hydroxybenzoic acid and glutaminylproline were shown as early biomarker for early puberty in girls, achieving area under the ROC curve of 0.71 and 0.72 in discriminating early puberty boys, and 0.70 and 0.74 in discriminating early puberty girls from controls. Through metabolomic analysis, we have identified metabolic perturbations and potential biomarkers of early puberty.