Metabolic biomarkers differentiate extrapulmonary tuberculosis from pulmonary TB and non-TB pleural effusions.

Tuberculosis (TB) is one of the leading causes of mortality in humans with clinical manifestations as pulmonary and extrapulmonary forms. TB pleural effusion (PITB) is one of the main forms of extrapulmonary TB, which is challenging to diagnose due to the overlapping clinical symptoms with other non-TB pleural effusions and poses severe complications in the treatment and management of disease. New biomarkers are urgently needed to improve the diagnostic accuracy for PlTB. Here we applied high-throughput targeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics using a 96-well plate format to profile metabolic signatures in serum and pleural fluid of PlTB patients. We identified taurine, glycine, tryptophan and kynurenine as the top metabolites for differentiation of PlTB from pulmonary TB and non-TB pleural effusions. Our work provides a new metabolomic assay for biomarker discovery and highlights metabolic signatures with potential to transform the diagnosis of PITB.