A Plasma Metabolic Signature to Diagnose Pulmonary Tuberculosis and Monitor Treatment Response

Background High-resolution metabolomics has shown promise for identifying blood-based biomarkers of tuberculosis (TB). We sought to discover a metabolic signature to detect pulmonary TB disease and monitor treatment response. Methods Plasma from Ethiopian persons with pulmonary TB at diagnosis (n = 82) was compared to household contacts with TB symptoms (n = 104) and 2, 6, and 12 months after treatment initiation. Participants were divided into training and test sets for model building, with additional validation using independent cohorts from the countries of Georgia (n = 89) and South Africa (n = 85). Signatures were further evaluated in nonhuman primates infected with Mycobacterium tuberculosis (Mtb). Results Among the metabolites that most significantly differed in concentration, tryptophan (Trp) and retinol were significantly decreased in persons with TB disease (45.2 vs 62.5 μM and 4.1 vs 8.2 μM, respectively), while kynurenine (Kyn) was significantly increased (2.1 vs 1.6 μM; q Conclusions The plasma Kyn/Trp ratio and retinol represents a promising metabolic signature that could advance TB diagnostics.