The Applications and Future of Blood-Based Metabolomics

As the most downstream omics discipline, metabolomics directly reflects an organism’s phenotype, capturing biochemical changes from disease, diet and environmental exposure. Unlike other omics approaches, though, the metabolome lacks standardized building blocks, making it more complex and diverse and as such, “uniquely suited for uncovering novel biomarkers and disease mechanisms,” Dr. Shuang Zhao, node manager and senior scientist at The Metabolomics Innovation Centre, told Technology Networks. 

“For certain diseases, genomic or proteomic alterations may not be evident, whereas metabolic disturbances are often more pronounced and detectable earlier,” Zhao explained. “Additionally, metabolites exhibit greater temporal sensitivity, offering timely insights into biological processes.”

“Blood-based metabolomics is extensively applied across diverse biomedical fields, including biomarker discovery, understanding disease mechanisms and precision medicine,” said Zhao. “Given that blood samples are frequently and routinely collected in clinical and laboratory settings, large-scale metabolomics studies with extensive patient cohorts are becoming increasingly feasible. This accessibility greatly facilitates the identification and validation of clinically useful biomarkers, ultimately accelerating their translation into diagnostic and therapeutic applications.”

Recent studies have identified the plasma metabolome as a promising source of biomarkers for Alzheimer’s disease, cancer, myalgic encephalomyelitis/ chronic fatigue syndrome and depression. 

In Alzheimer’s disease, researchers have correlated changes in brain tissue directly affected by Alzheimer’s progression with changes in the blood metabolome, indicating that the plasma metabolome reflects disease pathology and could in future be used to non-invasively monitor the disease. The team found 121 potential metabolites through nuclear magnetic spectroscopy analysis, several of which impact glucose oxidation, including lactic acid, pyruvate and glucose-6-phosphate. Other metabolites identified allude to oxidative stress resulting in brain dysfunction. 

Recent research has also pinpointed plasma metabolites as a promising avenue for diagnosis, staging and prognosis in multiple myeloma. Using ultra-high liquid chromatography-mass spectrometry, the researchers isolated 70 metabolites that underwent significant changes in newly diagnosed multiple myeloma patients compared to healthy controls. In their work, the authors identified a panel of plasma metabolite biomarkers, including lactic acid and leucine, that could also act as a tool for tumor surveillance.

By integrating evidence from large-scale studies, a recent review compiled 11 blood-based metabolites that are consistently altered in depression. They found that glutamic acid and phosphatidylcholine (32:0) were elevated in patients with depression, whereas levels of tryptophan, serotonin, creatinine, phenylalanine, valine, among others, were lower. 

Blood-based metabolomics, the challenges

However, translating the findings from blood-based metabolomics studies into the clinic is not without its challenges. 

Limitations in the reproducibility, validation and standardization of metabolomic biomarkers within diverse cohorts forms a barrier to their use in the clinic. 

“Advances in high-throughput, comprehensive analytical platforms, such as enhanced sensitivity mass spectrometry methods and standardized analytical workflows, are enabling more efficient and reproducible metabolomic profiling,” explained Zhao. “These developments facilitate larger-scale studies, improve data quality and strengthen biomarker validation, thus bridging the gap between metabolomics research and clinical practice.” 

“As these technological improvements continue, metabolomics is expected to increasingly impact precision medicine and diagnostics,” he continued. 

Zhao will be presenting at the Annual Society for Mass Spectrometry conference 2025, discussing The Metabolomics Innovation Centre's work, led by Dr. Xian Luo, on a newly developed small-scale, highly accurate and reproducible platform (SHARP), which allows the sensitive profiling of metabolites and lipids from just a single droplet of blood.  

“I'm particularly excited to share how this technology significantly enhances analytical sensitivity and precision, opening new possibilities for minimally invasive metabolomics studies, personalized diagnostics and clinical research,” Zhao told Technology Networks.