Exploratory Fecal Metabolomics Reveals Potential Metabolic Signatures Associated with GnRH Analog Treatment in Girls with Idiopathic Central Precocious Puberty

Background: This study utilized an untargeted metabolomics approach to preliminarily investigate changes in fecal metabolites in girls with idiopathic central precocious puberty (ICPP) before and after treatment with gonadotropin releasing hormone (GnRH) analogues. Methods: Matched fecal samples were collected from three groups: untreated girls with ICPP (ICPP-NT group), GnRH analogue-treated girls with ICPP (ICPP-T group), and a healthy control (HC) group. Differentially abundant metabolites were identified through untargeted metabolomics. Functional and pathway enrichment analyses were subsequently conducted. Furthermore, correlations between key metabolite levels and clinical indicators were evaluated. Results: Untargeted metabolomic analysis identified 1527 differentially abundant metabolites across the groups.The six most relevant pathways included Protein digestion and absorption, Aminoacyl-tRNA biosynthesis, Central carbon metabolism in cancer, D-Amino acid metabolism, Biosynthesis of amino acids, and ABC transporters. Twenty-eight core metabolites were screened from these pathways. Notably, the abundance changes of 14 metabolites, including L-lysine, L-histidine and its derivative histamine, and cadaverine, among others, showed significant associations with GnRH analogue treatment status. Clinical correlation analysis indicated that levels of L-phenylalanine and D-ornithine were correlated with both follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Conclusion: This study suggests that gut metabolism, particularly involving amino acids and their derivatives, may be linked to the pathophysiological mechanisms of ICPP and the response to treatment. These findings provide a preliminary foundation for developing diagnostic biomarkers and adjunct therapeutic strategies based on metabolic intervention.