Abstract
Diagnosing pulmonary tuberculosis (PTB) remains challenging, particularly in people living with HIV (PLWH) who have a high rate of false-negative tests using expectorated sputum. Urine, a non-invasive sample, offers a valuable source of metabolites reflecting systemic changes in disease. This study utilized liquid chromatography–mass spectrometry to investigate urinary biomarkers previously identified in other cohorts, using a well-characterized population of people newly-diagnosed with HIV who screened positive for TB symptoms in Port-au-Prince, Haiti. In this study, we identified a urinary metabolomic signature associated with PTB in PLWH, confirming significant elevations of ureidopropionic acid, 3-hydroxykynurenine, and m/z 115.0498. Untargeted metabolomic analysis revealed a putative isoform of hydroxytryptophan and kynurenic acid as additional PTB-associated metabolites. Four of these five metabolites were also significantly elevated in serum when clinically and microbiologically combined PTB groups were analyzed. Serum metabolite levels correlated positively with elevated blood C-reactive protein (CRP) and IL-6, key inflammatory markers associated with PTB pathology. Moreover, the diagnostic performance of urinary metabolites in participants with CD4+T count below 200 cells/mm³ was not different from that of CRP. Urine metabolomic profiling may complement a patient-centered approach, providing a non-invasive means for TB biomarker discovery and investigating the immunometabolic processes underlying TB in PLWH.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This project was funded by the Tri-Institutional Tuberculosis (TB) Research Advancement Center (TRAC) through the Developmental Project Award (Grant P30AI168433) and by the NIH Tuberculosis Research Units (TBRU) Network grant U19AI162584.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Institutional Review Boards (IRB) of the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) center in Port au Prince, Haiti, Weill Cornell Medical College, and Mass General Brigham gave ethical approval for this work. The biospecimen and data handling in this research were obtained from a previous study that strictly adhered to privacy and confidentiality standards. All participants provided written informed consent prior to their inclusion in the clinical cohort study and consented to the use of specimens for future research related to TB.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
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Data Availability
Supporting data are available with this publication and can be found in the Data Values file and the Supplementary Material. The supporting data include generated targeted and untargeted metabolomic datasets, cytokine values, a covariate table, and underlying values for figures.
