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- Title
Small molecule bio‐signature in childhood intra‐thoracic tuberculosis identified by metabolomics.
- 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
- Abstract
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.
- Subjects
SMALL molecules; METABOLOMICS; UNSATURATED fatty acids; TUBERCULOSIS; RIFAMPIN; CHOLINE; CHILD patients
- Publication
NMR in Biomedicine, 2023, Vol 36, Issue 9, p1
- ISSN
0952-3480
- Publication type
Article
- DOI
10.1002/nbm.4941