Multimodal plasma metabolomics and lipidomics in elucidating metabolic perturbations in tuberculosis patients with concurrent type 2 diabetes

Type 2 diabetes mellitus (DM) poses a major burden for the treatment and control of tuberculosis (TB). Characterization of the underlying metabolic perturbations in DM patients with TB infection would yield insights into the pathophysiology of TB-DM, thus potentially leading to improvements in TB treatment. In this study, a multimodal metabolomics and lipidomics workflow was applied to investigate plasma metabolic profiles of patients with TB and TB-DM. Significantly different biological processes and biomarkers in TB-DM vs. TB were identified using a data-driven, knowledge-based framework. Changes in metabolic and signaling pathways related to carbohydrate and amino acid metabolism were mainly captured by amide HILIC column metabolomics analysis, while perturbations in lipid metabolism were identified by the C18 metabolomics and lipidomics analysis. Compared to TB, TB-DM exhibited elevated levels of bile acids and molecules related to carbohydrate metabolism, as well as the depletion of glutamine, retinol, lysophosphatidylcholine, and phosphatidylcholine. Moreover, arachidonic acid metabolism was determined as a potentially important factor in the interaction between TB and DM pathophysiology. In a correlation network of the significantly altered molecules, among the central nodes, chenodeoxycholic acid was robustly associated with TB and DM. Fatty acid (22:4) was a component of all significant modules. In conclusion, the integration of multimodal metabolomics and lipidomics provides a thorough picture of the metabolic changes associated with TB-DM. The results obtained from this comprehensive profiling of TB patients with DM advance the current understanding of DM comorbidity in TB infection and contribute to the development of more effective treatment.