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

Abstract

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 household 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.

BCG‐induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next‐generation vaccines

“…Albeit relatively small, this study clearly shows the potential of proteomics for better understanding of early clearance, and the need for replication in other cohorts. Metabolomic studies in TB have mainly focused on diagnosis of LTBI and active TB, or on predicting progression to active disease, 188‐190 but one study in India found significantly higher concentrations of particular metabolites in household contacts compared to controls 191 . This is an interesting result, but unfortunately no data were provided on IGRA/TST among household contacts, so no conclusions can be made regarding early clearance.…”

Lymphocyte-Related Immunological Indicators for Stratifying Mycobacterium tuberculosis Infection

“…Multiple limitations registered by conventional tests of etiology hurdles to the timely diagnosis of disease and contribute to promote clinical progression as well as continued transmission. Recent advances in genomics (16,17), transcriptomics (18)(19)(20), proteomics (21)(22)(23), and metabolomics (24)(25)(26) have effectively facilitated the diagnosis of TB. But these emerging methods often require prohibitively complex equipment and operations, which hinder their promotion of clinical applications.…”

Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection

“…Nevertheless, these two tests were not useful in distinguishing ATB from LTBI (29)(30)(31). Moreover, a variety of host biomarkers identified by omics including transcriptome (32)(33)(34), proteome (35,36), and metabolome (37)(38)(39) have been proposed as potential biomarkers for diagnosing MTB infection. Howbeit, few studies validated their actual benefit in various areas with different demographic, ethnic settings, as well as TB prevalence.…”