Abstract
Profound tuberculosis (TB)-induced metabolic changes reflected in the blood metabolomic profile may provide an opportunity to identify specific markers of Mycobacterium tuberculosis infection. Using targeted liquid chromatography tandem mass spectrometry, we compared the levels of 30 small metabolites, including amino acids and derivatives, and small organic compounds in serum and M.tb antigen-stimulated whole blood cultures of active TB children, latent TB (LTBI) children, nonmycobacterial pneumonia (NMP) children, and healthy controls (HCs) to assess their potential as biomarkers of childhood TB. We found elevated levels of leucine and kynurenine combined with reduced concentrations of citrulline and glutamine in serum and blood cultures of TB and LTBI groups. LTBI status was additionally associated with a decrease in valine levels in blood cultures. The NMP metabolite profile was characterized by an increase in citrulline and glutamine and a decrease in leucine, kynurenine and valine concentrations. The highest discriminatory potential for identifying M.tb infection was observed for leucine detected in serum and kynurenine in stimulated blood cultures. The use of targeted metabolomics may reveal metabolic changes in M.tb-infected children, and the obtained results are a proof of principle of the usefulness of metabolites in the auxiliary diagnosis of TB in children.
Highlights
Profound tuberculosis (TB)-induced metabolic changes reflected in the blood metabolomic profile may provide an opportunity to identify specific markers of Mycobacterium tuberculosis infection
Considering that profound TB-induced metabolic changes reflected in the blood metabolic profile may provide an opportunity to identify specific markers of M.tb infection, in the present study, we used targeted tandem liquid chromatography–mass spectrometry (LC–MS/MS) to compare the levels of 30 small metabolites in serum and M.tb antigen-stimulated blood cultures of active TB children, latent M.tb infection (LTBI) children, infectious nonmycobacterial pneumonia (NMP) children and controls without active infection
Based on a comprehensive analysis of the results of the clinical and microbiological evaluation, the patients were divided into four groups: (1) children with active pulmonary TB (M.tb culture positive), (2) children with latent M.tb infection (LTBI) (M.tb culture-negative, interferon-gamma (IFN-γ) release assay (IGRA) positive), (3) children with infectious nonmycobacterial pneumonia without latent M.tb infection (NMP) (M.tb culture-negative, IGRA negative), and (4) healthy controls (HC) with no signs or symptoms of any lung diseases (IGRA negative)
Summary
Profound tuberculosis (TB)-induced metabolic changes reflected in the blood metabolomic profile may provide an opportunity to identify specific markers of Mycobacterium tuberculosis infection. Median and standard deviation of individual metabolites measured in serum and Mycobacterium tuberculosis antigen-stimulated whole blood QFT cultures, together with the p-value (uncorrected) of the Kruskal–Wallis test for equality of location parameter across study groups are presented in Supplementary Tables S1 and S2.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
