TY - JOUR KW - Mycobacterium leprae KW - Metabolomics KW - liquid chromatography–mass spectrometry KW - Biopsy KW - Paraffin Embedding KW - real-time PCR KW - Enzyme-Linked Immunosorbent Assay KW - leprosy AU - Pereira NV AU - Dornelas BDC AU - Costa WVTD AU - Zana JPS AU - Araújo ENDS AU - Rodrigues Campos FDA AU - Campos DRDO AU - Silva TDC AU - Souza HOAD AU - Martins MM AU - Goulart Filho LR AU - Goulart IMB AB - Leprosy presents a broad clinical–immunological spectrum, whose heterogeneity challenges early diagnosis and disease stratification. Metabolomic approaches have emerged as promising tools for identifying potential biomarkers associated with the disease’s pathophysiology. This study aimed to investigate metabolic profiles associated with the different clinical forms of leprosy using untargeted metabolomics in formalin-fixed paraffin-embedded (FFPE) tissue samples. A retrospective cross-sectional study was conducted with 55 patients classified according to the Ridley–Jopling spectrum. Metabolites were extracted from FFPE skin biopsies and analyzed by liquid chromatography–mass spectrometry (LC-MS). From 908 metabolites initially detected, 27 were retained after frequency filtering. Six metabolites ultimately met the criteria of one-way analysis of variance (ANOVA, p < 0.05) and fold-change (FC ≥ 2.0) for differential expression, while N-stearoyl tryptophan was identified as an additional candidate metabolite based on its contribution to multivariate group discrimination. These included 11-hydroperoxy-H4-neuroprostane, which showed a specific association with bacterial load, and the Gly-Pro-Lys tripeptide, which correlated with markers of infection progression. Metabolomics applied to FFPE samples proved feasible for discriminating the clinical spectrum of leprosy and annotating signatures associated with immune response. This approach represents an innovative strategy for exploratory biomarker discovery using archived histopathological samples in translational research. BT - Microorganisms DA - 07/2026 DO - 10.3390/microorganisms14071567 IS - 7 LA - ENG M3 - Article N2 - Leprosy presents a broad clinical–immunological spectrum, whose heterogeneity challenges early diagnosis and disease stratification. Metabolomic approaches have emerged as promising tools for identifying potential biomarkers associated with the disease’s pathophysiology. This study aimed to investigate metabolic profiles associated with the different clinical forms of leprosy using untargeted metabolomics in formalin-fixed paraffin-embedded (FFPE) tissue samples. A retrospective cross-sectional study was conducted with 55 patients classified according to the Ridley–Jopling spectrum. Metabolites were extracted from FFPE skin biopsies and analyzed by liquid chromatography–mass spectrometry (LC-MS). From 908 metabolites initially detected, 27 were retained after frequency filtering. Six metabolites ultimately met the criteria of one-way analysis of variance (ANOVA, p < 0.05) and fold-change (FC ≥ 2.0) for differential expression, while N-stearoyl tryptophan was identified as an additional candidate metabolite based on its contribution to multivariate group discrimination. These included 11-hydroperoxy-H4-neuroprostane, which showed a specific association with bacterial load, and the Gly-Pro-Lys tripeptide, which correlated with markers of infection progression. Metabolomics applied to FFPE samples proved feasible for discriminating the clinical spectrum of leprosy and annotating signatures associated with immune response. This approach represents an innovative strategy for exploratory biomarker discovery using archived histopathological samples in translational research. PB - MDPI AG PY - 2026 SP - 1 EP - 21 T2 - Microorganisms TI - Mass Spectrometry-Based Metabolomics in Formalin-Fixed Paraffin-Embedded Skin Biopsies Identifies Potential Candidate Biomarkers for Leprosy Progression Across the Ridley–Jopling Clinical Spectrum UR - https://www.mdpi.com/2076-2607/14/7/1567/pdf?version=1784286197 VL - 14 SN - 2076-2607 ER -