Untargeted metabolomics of pulmonary tuberculosis patient serum reveals potential prognostic markers of both latent infection and outcome

Abstract

Currently, there are no particularly effective biomarkers to distinguish between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB) and evaluate the outcome of TB treatment. In this study, we have characterized the changes in the serum metabolic profiles caused by Mycobacterium tuberculosis (Mtb) infection and standard anti-TB treatment with isoniazid–rifampin–pyrazinamide–ethambutol (HRZE) using GC-MS and LC-MS/MS. Seven metabolites, including 3-oxopalmitic acid, akeboside ste, sulfolithocholic acid, 2-decylfuran (4,8,8-trimethyldecahydro-1,4-methanoazulen-9-yl)methanol, d-(+)-camphor, and 2-methylaminoadenosine, were identified to have significantly higher levels in LTBI and untreated PTB patients (T0) than those in uninfected healthy controls (Un). Among them, akeboside Ste and sulfolithocholic acid were significantly decreased in PTB patients with 2-month HRZE (T2) and cured PTB patients with 2-month HRZE followed by 4-month isoniazid-rifampin (HR) (T6). Receiver operator characteristic curve analysis revealed that the combined diagnostic model showed excellent performance for distinguishing LT from T0 and Un. By analyzing the biochemical and disease-related pathways, we observed that the differential metabolites in the serum of LTBI or TB patients, compared to healthy controls, were mainly involved in glutathione metabolism, ascorbate and aldarate metabolism, and porphyrin and chlorophyll metabolism. The metabolites with significant differences between the T0 group and the T6 group were mainly enriched in niacin and nicotinamide metabolism. Our study provided more detailed experimental data for developing laboratory standards for evaluating LTBI and cured PTB.

Variations in Quinolinic Acid Levels in Tuberculosis Patients with Diabetes Comorbidity: A Pilot Prospective Cohort Study

“…Metabolomic analysis may lead to the identification of potential biomarkers for diagnostic and therapeutic purposes. 13 Diabetes is a chronic metabolic disorder characterized by alterations in carbohydrate, lipid, and protein metabolism. 14 Immune-metabolic dysregulation in diabetic patients is closely associated with susceptibility to tuberculosis.…”

Human Archaeological Dentin as Source of Polar and Less Polar Metabolites for Untargeted Metabolomic Research: The Case of Yersinia pestis

“…Metabolites are small molecules (<1.5 kilo Daltons (kDa)) produced as by-products of cellular metabolism and can be studied using several approaches including Fourier-transform infrared (FTIR), mass spectrometry (MS) or nuclear magnetic resonance (NMR) spectroscopy, among several others. They can be found in any cellular material or material with cellular contact including blood, urine, hair, bone and soft tissue (for example see [ 14 , 15 , 16 ]). Metabolomic studies can be either targeted or untargeted and are a primary focus for disease biomarker discovery (reviewed in [ 17 ]).…”