Recent advances in metabolomics of mycobacteria and tuberculosis: From species differentiation to pharmacometabolomics and personalized therapy

Given its integral role in medicinal chemistry and frequent application within multi-omics strategies, metabolomics provides essential contributions to both the development of novel therapeutics and the optimization of existing drug regimens. This review presents diverse and recent applications of metabolomics closely related to Mycobacterium and tuberculosis (TB). It summarizes recent advances in metabolomics-based research which supports the understanding of the causative agent and the infection process. The applications of metabolomics cover understanding the host response to Mycobacterium tuberculosis (MtB) virulence, differentiation of Mycobacterium strains, uncovering the role of cellular components and networks, determination of bacterial response to stress, description of metabolites and metabolic pathways critical for early adaptive responses, understanding resistance, including the identification of drug-resistant TB, and profiling the mode of action. Moreover, pharmacometabolomics and the use of artificial intelligence (AI) show that personalized medicine may be a key in TB treatment strategy. The review summarizes pharmacometabolomic studies of first- and second-line antimycobacterial drugs, highlighting treatment-associated changes in lipid, amino acid, and energy metabolism linked to patient responsiveness, bacterial clearance, comorbid metabolic or inflammatory conditions, host genetic background, and the risk of adverse drug reactions. It will also support the future research exploring the influence of environmental and nutritional factors on bacterial metabolism and disease outcomes, which is required to deepen the understanding of the complex host-microbe interactions.