Potential biomarkers for tuberculous meningitis diagnosis using metabolomics and proteomics: a systematic review

Tuberculosis (TB) is the leading cause of death from a single infectious agent, with approximately 1.2 million deaths reported in 2023. While TB primarily affects the lungs, it can also spread to other organs, where it is classified as extrapulmonary TB. Tuberculous meningitis (TBM) is the most severe form of extrapulmonary TB, affecting 1–5% of TB cases. Delayed diagnosis contributes to its high mortality and severe neurological complications, with approximately 10% of affected individuals dying or suffering permanent neurological damage. When combined with adjunctive therapy, early detection and treatment can significantly improve survival outcomes. Currently, many studies have identified potential biomarkers of TBM; however, to date, there is no clear consensus on the markers altered in TBM. Hence, we conducted a systematic review aimed at identifying metabolites and proteins that are significantly altered in TBM when compared with healthy controls. Three databases — PubMed, Scopus, and Web of Science — were scanned by two independent reviewers for potential articles that met our inclusion and exclusion criteria. After quality assessment, 17 studies were included, comprising a total of 963 participants (healthy control, n = 576; TBM, n = 387). Metabolites and proteins identified as being significantly altered across studies included alanine, isoleucine, myo-inositol, valine, arachidonate 5-lipoxygenase (ALOX5), apolipoprotein B (APOB), and glial fibrillary acidic protein (GFAP), which were detected in serum, urine, brain tissue, and cerebrospinal fluid samples. These markers have potential diagnostic value for TBM. However, further validation is needed to determine their specificity to reliably distinguish TBM from other neurological infections, which could improve early diagnosis and patient outcomes in TBM.