Serum untargeted metabolomics reveals distinct metabolic signatures and potential biomarkers in female and latent genital tuberculosis

Female genital tuberculosis (FGTB) and latent genital tuberculosis (LGTB) critically impair women's reproductive health. However, their early diagnosis and treatment remain challenging due to nonspecific symptoms and suboptimal diagnostic methods. This study utilized serum untargeted metabolomics to identify metabolic signatures and potential biomarkers in 21 participants (9 FGTB, 6 LGTB, 6 controls), aiming to provide valuable references for early diagnosis and exploration of the pathogenesis of these diseases. Multivariate and univariate analyses identified 8 and 13 differential metabolites in FGTB and LGTB groups, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed these differential metabolites were primarily enriched in lipid-related pathways (steroid hormone biosynthesis, bile secretion) and amino acid/nucleic acid metabolism (purine/tryptophan pathways). Notably, the variable importance of projection (VIP) and receiver operating characteristic (ROC) analyses revealed deoxyschizandrin, estrone-3-sulfate and toosendanin demonstrated exceptional diagnostic accuracy for FGTB (VIP > 3, P < 0.05, and the area under the ROC curve (AUC) > 0.9), while dyclonine emerged as a robust LGTB biomarker (AUC = 0.944). These findings highlight systemic metabolic dysregulation in FGTB/LGTB and propose serum-based biomarkers as noninvasive tools for early diagnosis. The study pioneers the application of serum untargeted metabolomics in FGTB/LGTB, offering novel insights into pathogenesis and therapeutic targets.