Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study

Area of Science:

• Metabolomics
• Infectious Diseases
• Biochemistry

Background:

• Tuberculosis (TB) remains a global health challenge, necessitating novel diagnostic biomarkers and therapeutic targets.
• Understanding the host-pathogen metabolic interplay is crucial for developing effective anti-TB strategies.

Purpose of the Study:

• To characterize plasma metabolites in active TB disease and identify novel pathophysiologic pathways.
• To discover biomarkers for TB onset, progression, and resolution.
• To inform the development of new anti-tuberculosis drugs.

Main Methods:

• Untargeted metabolomic analysis using liquid chromatography high-resolution mass spectrometry (LC-MS) on plasma samples.
• Statistical and bioinformatics analyses to identify significantly different metabolites (FDR q<0.05).
• Hierarchical cluster analysis (HCA) and LC-MS/MS for metabolite identification and confirmation.

Main Results:

• Over 23,000 metabolites detected; 61 significantly differed between TB patients and controls.
• Identified upregulated metabolites in TB patients, including glutamate, choline derivatives, Mtb-derived glycolipids (trehalose-6-mycolate, phosphatidylinositol), and resolvins (RvD1, RvD2).
• Metabolomic analysis successfully differentiated active TB patients from asymptomatic household contacts.

Conclusions:

• High-resolution metabolomics can distinguish active TB disease from asymptomatic infection.
• Upregulated metabolites, particularly Mtb-derived glycolipids and resolvins, show potential as TB biomarkers.
• These findings may elucidate pathways involved in TB pathogenesis and resolution, guiding therapeutic development.