Host lipidome and tuberculosis treatment failure

Area of Science:

• Lipidomics
• Tuberculosis Pathogenesis
• Biomarker Discovery

Background:

• Host lipids are integral to tuberculosis (TB) pathogenesis.
• The influence of host lipids at TB treatment initiation on treatment outcomes remains under-explored.
• Unbiased lipidomics can reveal associations between host lipids and TB treatment failure.

Purpose of the Study:

• To prospectively investigate the association between baseline host lipid profiles and the risk of TB treatment failure.
• To identify specific lipids that can serve as predictors of TB treatment outcomes.
• To explore the potential of lipid signatures for risk stratification and therapeutic monitoring in TB patients.

Main Methods:

• A case-control study (n=192) nested within a prospective cohort of adults with pulmonary TB.
• Plasma lipids were quantified using liquid chromatography-mass spectrometry.
• Machine learning algorithms identified lipids with high predictive value (Area Under the Curve - AUC) for TB treatment failure.

Main Results:

• Thirty-two lipids showed significant differences between patients who failed treatment and controls.
• Lower baseline levels of cholesteryl esters and oxylipins, and higher levels of ceramides and triglycerides were associated with treatment failure.
• A classifier model using two cholesteryl ester lipids achieved an AUC of 0.79 for predicting TB treatment failure.

Conclusions:

• Specific baseline host lipids are associated with TB treatment failure.
• A novel lipid signature demonstrates prognostic accuracy for predicting TB treatment failure.
• Identified lipids represent potential targets for risk stratification, adjunct therapies, and treatment monitoring in tuberculosis management.