Post-therapy metabolic profiles of tuberculosis patients with treatment-cured and treatment-failed outcomes

Introduction: Despite effective tuberculosis (TB) treatment, approximately 1.5 million individuals still experience treatment failure annually. The drug-induced metabolic effects of TB treatment, particularly after treatment cessation, remain poorly understood. This pilot study investigated post-therapy alterations in the urinary metabolome of drug-susceptible pulmonary TB patients with either cured or failed treatment outcomes.

Methods: A pretest-posttest study design was used, with urine samples collected at diagnosis (pre-therapy) and after treatment cessation (Week 26, post-therapy) from the same patients. Amino acid analysis (gas chromatography-mass spectrometry) and proton nuclear magnetic resonance were applied to characterise metabolic shifts in treatment-cured (n=14) and treatment-failed (n=10) patient groups. Differential metabolites were identified using the Wilcoxon signed-rank test (FDR-adjusted p<0.1), with visualisation by boxplots and line graphs.

Results: Significant metabolic alterations were observed only in the treatment-cured group, with consistent post-therapy changes in fumaric acid, methylamine, and formic acid. Similar but less consistent trends were seen in the treatment-failed group, where variability and limited sample size may have obscured significance. Although not differential in either outcome group, amino acids or related derivatives generally declined post-therapy in the treatment-cured group, with this trend less pronounced in the treatment-failed group.

Conclusion: The observed shifts reflect not only disease resolution but also persistent treatment-related effects, particularly linked to isoniazid. These findings reveal that isoniazid influences the urinary metabolome beyond treatment cessation, regardless of outcome. Overall, the results underscore the intertwined roles of disease resolution, drug exposure, and microbiome interactions in shaping host metabolism after TB treatment.