Integrated Plasma LC-MS Metabolomics and Immunological Profiling Identifies Potential Biomarkers for Latent and Active Tuberculosis

Background Latent tuberculosis infection (LTBI) and active tuberculosis (ATB) represent distinct clinical states within the tuberculosis disease spectrum, yet reliable biomarkers for disease staging remain limited. We investigated whether plasma metabolic profiling could characterize stage-associated alterations and their relationship with T-cell immunity. Methods In this case–control study, plasma samples from healthy controls (HC), LTBI, and ATB individuals (n = 12 per group) were analyzed using untargeted UHPLC–Orbitrap LC–MS. Peripheral T-cell subsets were quantified by flow cytometry. Multivariate analysis, pathway enrichment, receiver operating characteristic (ROC) analysis, and correlation analysis were performed to identify discriminatory metabolites and immune–metabolic associations. Results A total of 1,592 metabolites were detected. Distinct metabolic patterns were observed across groups, with LTBI exhibiting an intermediate profile between HC and ATB. Lipid-related pathways, including bile secretion and glycerophospholipid metabolism, were prominently altered in ATB. Ten candidate metabolites demonstrated strong discriminatory performance. Fatty acid oxidation–related metabolites were positively associated with CD4⁺ and CD8⁺ T-cell counts, whereas bile acid–related metabolites showed inverse correlations. Conclusion Plasma metabolomic profiling identifies stage-associated metabolic signatures linked to T-cell immunity, providing potential biomarkers for distinguishing LTBI from ATB. Trial registration: Not applicable. This study is an observational case-control study and does not involve requirements for prospective interventional clinical trial registration.