Applications of Untargeted Metabolomics

Non-targeted metabolomics is a research method that involves systematic and comprehensive analysis of the entire metabolome to obtain large amounts of metabolite data, and subsequently identify differential metabolites, based on limited relevant research and background knowledge. Currently, non-targeted metabolomics is widely used in the discovery of biomarkers, disease diagnosis, and mechanism research. It provides new ideas and directions for solving bottleneck problems in some disease mechanism research.

1. Non-targeted metabolomics reveals potential targets for cardiovascular disease treatment

Elevated levels of trimethylamine N-oxide (TMAO) cause abnormal lipid accumulation, increasing the risk of developing cardiovascular disease. Non-targeted metabolomics analysis of patients with cardiovascular disease showed a significant increase in TMAO levels in their plasma. Choline-containing substances ingested from food can be metabolized to TMA in the gut microbiome via choline TMA lyase, which is then further metabolized to TMAO in the liver through flavin-containing monooxygenase 3 (FMO3) catalysis.

Further research revealed that transgenic mice overexpressing FMO3 had significantly higher TMAO levels in their plasma under the same high-choline diet conditions as wild-type mice. Mice with silenced FMO3 expression using antisense oligonucleotide technology had significantly lower TMAO levels in their plasma than the control group, indicating that FMO3 can further affect the pathogenesis of atherosclerosis and other cardiovascular diseases by regulating plasma TMAO levels. The above research based on non-targeted metabolomics suggests that FMO3 may be a potential target for the treatment of cardiovascular disease.

2. Non-targeted metabolomics reveals potential targets for cancer treatment

Using capillary electrophoresis-mass spectrometry, untargeted metabolomics analysis was conducted on neuroglioma samples, revealing significantly higher levels of taurine in the tumour tissue than in the adjacent control tissue, positively correlated with glioma grading (malignancy). Molecular docking simulations showed that taurine can competitively inhibit the catalytic activity of proline hydroxylase, affecting the degradation of hypoxia-inducible factor-1α and promoting its nuclear entry, thereby initiating the expression of many tumour-related genes.

Thus, increasing intracellular taurine content can promote tumor occurrence and development. The study found that intracellular taurine is synthesized from cysteine as a precursor, and cysteine needs to be transported into the cell through cysteine or glutamate reverse transporter. Inhibiting this transporter can block the biosynthesis of taurine, thereby inhibiting the proliferation and invasion of tumor cells. Therefore, the cysteine or glutamate reverse transporter may be a potential target for the treatment of neuroglioma. In a study of acute myeloid leukemia, a combination of tyrosine kinase inhibitors and taurine led to a significant reduction in leukemia cell viability, suggesting that taurine may also be a potential target for leukemia treatment.