Urinary metabolite markers characterizing tuberculosis treatment failure

Abstract

Background Considering that approximately 15% of the nine million new tuberculosis (TB) cases reported per annum are not treated successfully, new, distinctive and specific biomarkers are needed to better characterize the biological basis of a poor treatment outcome. Methods Urine samples from 41 active pulmonary TB patients were collected at baseline (time of diagnosis), during treatment (weeks 1, 2 and 4) and 2 weeks after treatment completion (week 26). These samples were divided into successful (cured) and unsuccessful (failed) treatment outcome groups and analyzed using a GCxGC-TOFMS metabolomics research approach. Results The metabolite data collected showed clear differentiation of the cured and failed treatment outcome groups using the samples collected at the time of diagnosis, i.e. before any treatment was administered. Conclusions The treatment failure group was characterized by an imbalanced gut microbiome, in addition to elevated levels of metabolites associated with abnormalities in the long-chain fatty acid β-oxidation pathway, accompanied by reduced l-carnitine and short-chain fatty acids, indicative of a mitochondrial trifunctional protein defect in particular. Furthermore, an altered amino acid metabolism was also observed in these patients, which confirms previous findings and associations to increased interferon gamma due to the host’s immune response to M. tuberculosis and a compromised insulin secretion