Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort

Background: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. Methods: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired H-1 NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni-and multivariate statistical analysis. Results: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. Conclusion: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.