Metabolomic Biomarkers in Tuberculosis Diagnosis and Treatment

Metabolomic biomarkers offer a window into host–pathogen interactions in tuberculosis (TB), enabling the detection of disease, risk stratification of latent infection and monitoring of treatment response. By profiling small molecules in biofluids such as serum, plasma or urine, researchers can identify characteristic metabolic signatures—panels or ratios of amino acids, lipids and other metabolites—that distinguish active TB from latent infection or healthy states. These signatures reflect inflammatory pathways, lipid remodelling and energy metabolism alterations driven by Mycobacterium tuberculosis and the host immune response. Advances in high-resolution mass spectrometry and machine-learning algorithms have yielded predictive models with high diagnostic accuracy, while evolving biosignatures promise early detection of subclinical disease months before symptom onset. Integration of metabolomic data with conventional immunodiagnostic tests, such as interferon-γ release assays, and with emerging vesicle-based assays, has the potential to expedite treatment initiation, tailor therapy duration and monitor therapeutic efficacy in diverse global settings.

Research from Nature Portfolio

One seminal study established a trans-African metabolic biosignature by analysing serum and plasma samples from TB-exposed individuals. It revealed a set of metabolites whose concentration changes could predict progression to active disease up to a year before clinical diagnosis, achieving moderate sensitivity and specificity across multiple sites. This work underpinned the concept of pre-symptomatic metabolic alterations and demonstrated the feasibility of metabolic risk stratification in high-burden regions. A complementary investigation employed targeted liquid chromatography–tandem mass spectrometry to compare serum metabolite profiles in active TB patients, individuals with latent infection and healthy controls. It identified elevated glutamate, sulfoxy methionine and aspartate alongside reduced glutamine, methionine and asparagine in active disease. Metabolite ratios such as glutamate/glutamine and sulfoxy methionine/methionine provided robust discrimination and hold promise as adjunctive, rapid, non-invasive diagnostic tools.

Metabolomic Biomarkers in Tuberculosis Diagnosis and Treatment publication trend

The graph below shows the total number of articles in metabolomic biomarkers in tuberculosis diagnosis and treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolomics: The comprehensive study of small molecules (metabolites) in biological systems, reflecting physiological and pathological states.

Biomarker: A measurable indicator of a biological or pathological process, used for diagnosis, prognosis or monitoring treatment response.

Mass spectrometry (MS): An analytical technique that measures mass-to-charge ratios of ions to identify and quantify molecules in complex samples.

Liquid chromatography–tandem mass spectrometry (LC-MS/MS): A two-step method combining liquid chromatographic separation with mass spectrometric detection, enabling precise metabolite quantification.

Exosome: A small extracellular vesicle released by cells, containing proteins, lipids and nucleic acids that reflect the cell’s metabolic and signalling state.

References

1. Automated Diagnosis and Phenotyping of Tuberculosis Using Serum Metabolic Fingerprints. Advanced Science (2024).
2. Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients. Emerging Microbes & Infections (2024).
3. Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases. International Journal of Molecular Sciences (2024).
4. Metabolite changes in blood predict the onset of tuberculosis. Nature Communications (2018).
5. Identification of serum biomarkers for active pulmonary tuberculosis using a targeted metabolomics approach. Scientific Reports (2020).