Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers

Although 23% of world population is infected with Mycobacterium tuberculosis ( M. tb ), only 5-10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb .-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb .-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb .-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81-1.00, p -value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.