Urine metabolites flag tuberculosis in people living with HIV

Diagnosing pulmonary tuberculosis (PTB) is especially difficult in people living with HIV (PLWH), who often have false-negative tests when clinicians rely on expectorated sputum. To address this problem, researchers turned to urine, a non-invasive sample that can reflect systemic changes in disease and is easier to collect than sputum. In a well-characterized group of people newly-diagnosed with HIV who screened positive for TB symptoms in Port-au-Prince, Haiti, the team led by corresponding author Kyu Y. Rhee looked for metabolic fingerprints of TB in urine. The goal was to test whether metabolites previously reported in other studies could distinguish PTB in this high-risk population, and whether those signals linked to known inflammatory processes. By focusing on metabolites that can be measured without invasive procedures, the study aimed to move toward patient-centered approaches that could be practical in settings where sputum testing is unreliable or difficult to obtain. The work reported here used established metabolomic tools to probe whether a urine-based signature could add clinically useful information about TB in people with HIV.

The study used liquid chromatography-mass spectrometry to search for urinary biomarkers that had been identified in other cohorts, applying both targeted and untargeted metabolomic analyses. In the urine of participants with pulmonary TB, investigators confirmed significant elevations of ureidopropionic acid, 3-hydroxykynurenine, and m/z 115.0498. Untargeted analysis further revealed a putative isoform of hydroxytryptophan and kynurenic acid as additional PTB-associated metabolites. When serum from the same participants was examined, four of these five metabolites were also significantly elevated in analyses that combined clinically and microbiologically defined PTB groups. Importantly, serum metabolite levels correlated positively with elevated blood C-reactive protein (CRP) and IL-6, linking the metabolite findings to key inflammatory markers associated with PTB pathology. The authors also reported that the diagnostic performance of the urinary metabolites in participants with CD4+T count below 200 cells/mm³ was not different from that of CRP, suggesting comparable utility in people with advanced immune suppression.

These findings suggest that urine metabolomic profiling could serve as a complementary, non-invasive approach for TB biomarker discovery and for studying the immune-linked metabolic changes that accompany PTB in PLWH. The association between the identified metabolites and the C-reactive protein-IL-6 axis points to a connection between the metabolic signature and the inflammatory response that characterizes TB disease. Because urine is easier to collect than sputum, a validated urine-based panel could help reduce missed diagnoses in people who cannot produce reliable sputum samples, including many with advanced HIV. The observation that urinary metabolites performed similarly to CRP in people with CD4+T count below 200 cells/mm³ raises the possibility that metabolite testing could be useful even in those with severe immune suppression. Overall, the study supports further work to refine and validate urine metabolite markers and to explore how they might be integrated into patient-centered strategies for TB detection and monitoring among people living with HIV.