Lipidomics for Tuberculosis Biomarker Discovery: A Scoping Review of Human, Animal, Ex Vivo, and In Vitro Evidence

Tuberculosis (TB) remains a leading global infectious cause of death. While host lipidomics offers a promising frontier for biomarker discovery, the evidence base remains fragmented across heterogeneous study models, biological matrices, and analytical platforms. This scoping review systematically maps the landscape of TB host lipidomics to identify methodological trends, established knowledge clusters, and translational bottlenecks. Guided by the PRISMA-ScR and the PCC JBI (Joanna Briggs Institute) frameworks, a structured search was conducted across PubMed, Europe PMC, OpenAlex, and Google Scholar. The review protocol was prospectively registered on the Open Science Framework (OSF Protocol: 10.17605/OSF.IO/5EGMR). Forty-eight primary empirical studies published between 2014 and 2026 were selected for descriptive numerical analysis and thematic synthesis. Research is highly centralized in low- and middle-income countries (85.4%), with China, India, and South Africa acting as primary hubs. Methodological analysis revealed a heavy reliance on blood-based matrices (64.6% plasma/serum), with truly non-invasive matrices, urine and exhaled breath, accounting for only 14.6% of studies with liquid chromatography-mass spectrometry accounting for (77.1% LC-MS/MS). Glycerophospholipids (66.7%) and sphingolipids (43.8%) emerged as the most consistent systemic metabolic signatures of active disease. However, a severe longitudinal data deficit exists: 64.6% of studies are restricted to cross-sectional diagnostic discovery, while only 12.5% address treatment monitoring or prognosis. Critically, 70.8% of the evidence base lacked independent cohort validation, and no studies correlated host lipid profiles with direct measures of TB infectiousness. TB lipidomics has achieved technical maturity in initial diagnostic discovery but remains poorly optimized for longitudinal patient management and transmission control. A critical knowledge gap is the total absence of data linking host lipid signatures to aerobiologic measures of transmission potential, such as Cough Aerosol Culture (CAC) positivity. As primary disease burden hubs and research volume, LMICs are uniquely positioned to lead this next translational phase of prospective longitudinal validation. Advancing the field requires a deliberate reorientation toward specimen types and study designs capable of capturing the biology of the lung-airway interface, the anatomical origin of infectious aerosols. Prospective studies correlating systemic and localized lipid signatures with CAC-defined infectiousness in transmission cohorts represent an essential and entirely unexplored frontier for host-directed TB biomarker science.