Identification of potential lipid biomarkers for active pulmonary tuberculosis using ultra-high-performance liquid chromatography-tandem mass spectrometry

Abstract

Early diagnosis of active pulmonary tuberculosis (TB) is the key to controlling the disease. Host lipids are nutrient sources for the metabolism of Mycobacterium tuberculosis. In this research work, we used ultra-high-performance liquid chromatography-tandem mass spectrometry to screen plasma lipids in TB patients, lung cancer patients, community-acquired pneumonia patients, and normal healthy controls. Principal component analysis, orthogonal partial least squares discriminant analysis, and K-means clustering algorithm analysis were used to identify lipids with differential abundance. A total of 22 differential lipids were filtered out among all subjects. The plasma phospholipid levels were decreased, while the cholesterol ester levels were increased in patients with TB. We speculate that the infection of M. tuberculosis may regulate the lipid metabolism of TB patients and may promote host-assisted bacterial degradation of phospholipids and accumulation of cholesterol esters. This may be related to the formation of lung cavities with caseous necrosis. The results of receiver operating characteristic curve analysis revealed four lipids such as phosphatidylcholine (PC, 12:0/22:2), PC (16:0/18:2), cholesteryl ester (20:3), and sphingomyelin (d18:0/18:1) as potential biomarkers for early diagnosis of TB. The diagnostic model was fitted by using logistic regression analysis and combining the above four lipids with a sensitivity of 92.9%, a specificity of 82.4%, and the area under the curve (AUC) value of 0.934 (95% CI 0.873 – 0.971). The machine learning method (10-fold cross-validation) demonstrated that the model had good accuracy (0.908 AUC, 85.3% sensitivity, and 85.9% specificity). The lipids identified in this study may serve as novel biomarkers in TB diagnosis. Our research may pave the foundation for understanding the pathogenesis of TB.

Using Omics to Study Leprosy, Tuberculosis, and Other Mycobacterial Diseases

“…This approach demonstrated that TB patients had increased cholesterol levels and decreased plasma phospholipid levels. This study confirms that lipids such as phosphatidylcholine, cholesteryl ester and sphingomyelin are promising biomarkers for the early detection of TB (Han et al, 2021).…”

“…After entry into the host cell, Mtb utilizes host lipids as a primary nutrient source. Mtb infection regulates TB patients lipid metabolism and favors the degradation of phospholipids and accumulation of cholesterol esters, resulting in cavities with caseous necrosis in the lungs ( Han et al., 2021 ). Mtb also utilized lipids in the development of multi-drug resistance (MDR).…”

Novel Potential Diagnostic Serum Biomarkers of Metabolomics in Osteoarticular Tuberculosis Patients: A Preliminary Study

“…Moreover, it also reported increased eicosanoid ratios in plasma in tuberculosis patients compared to healthy control (Mayer-Barber and Sher, 2015). However, related research about the lipid in osteoarticular tuberculosis or even other extrapulmonary tuberculosis is rare; the results of our research, whether from the differential metabolites screened out or the signal pathways obtained from bioinformatics, are closely related to the results of pulmonary tuberculosis-related research (Huang et al, 2020;Han et al, 2021). It provides more reference value for future research on diagnostic biomarkers from the perspective of metabolomics and provides some hints for the establishment of subsequent auxiliary diagnostic methods for these differential metabolites.…”

Biomarker discovery for tuberculosis using metabolomics

“…In 2019, Huang et al (2019) did plasma metabolic profiling for cohorts of HCs (n = 35) and patients with TB (n = 35), CAP (n = 35), and lung cancer (LC) (n = 31), and found three differential plasma metabolites (Xanthine, 4-Pyridoxate, and D-glutamic acid) as potential biomarkers for pulmonary TB. Recently this same group ( Han et al, 2021 ) reported decreased plasma phospholipid levels and increased cholesteryl ester (CE) levels in patients with TB. Four lipids [PC (12:0/22:2), PC (16:0/18:2), CE (20:3), and SM (d18:0/18:1)] were identified as potential biomarkers for early diagnosis of TB, with a combined high differentiating capability (AUC≥0.91).…”