Small molecule bio‐signature in childhood intra‐thoracic tuberculosis identified by metabolomics

• Published in: NMR in biomedicine 2023-09, Vol.36 (9), p.e4941-n/a
• Main Authors: Sharma, Nupur, Upadhyay, Deepti, Gautam, Hitender, Sharma, Uma, Lodha, Rakesh, Kabra, Sushil Kumar, Das, Bimal Kumar, Kapil, Arti, Mohan, Anant, Jagannathan, Naranamangalam Raghunathan, Guleria, Randeep, Singh, Urvashi Balbir
• Format: Article
• Language: English
• Subjects: 1H NMR spectroscopy; Abnormalities; Acetic acid; Biological products; biomarkers; childhood TB; Children; Choline; Creatine; Deregulation; Dimethylglycine; Fatty acids; Glutamine; Histidine; Inflammation; intra‐thoracic TB; Lipid metabolism; Lipids; Lysine; Magnetic resonance spectroscopy; Metabolic pathways; Metabolism; Metabolites; Metabolomics; NMR spectroscopy; Pediatrics; Phenylalanine; Phosphocreatine; Polyunsaturated fatty acids; Protein biosynthesis; Protein synthesis; Thorax; Tuberculosis
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.4941

The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture‐confirmed intra‐thoracic TB (ITTB) (n = 23) and compared it with those of non‐TB controls (NTCs) (n = 13) using proton NMR spectroscopy‐based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N‐α‐acetyl‐lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti‐inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population. 1H NMR spectroscopy‐based targeted and untargeted metabolomics approaches coupled with multivariate analysis were used to investigate TB‐specific biomarkers by comparing serum metabolites of children with culture‐confirmed TB and non‐TB subjects. Results indicated significant changes in metabolism of culture‐confirmed TB children with disturbances in metabolites associated with protein synthesis, anti‐inflammatory and cytoprotective mechanisms, membrane metabolism, energy generation processes, and fatty acid and lipid metabolisms.