Precision and progress: Oxford scientists create next-gen tech for metabolomics

Oxford University researchers have created a new method for large-scale metabolite analysis in biological samples. The UK scientists state that the new technology can be applied to metabolomics, such as studying gut microbiome metabolism, the effects of antimicrobial resistance on bacterial processes, or identifying biomarkers for early cancer detection.

Their study in Nature Protocols shows how the method involves anion-exchange chromatography coupled to mass spectrometry (AEC-MS), which improves the analysis of metabolites in cells, tissues, and biofluids that drive main metabolic pathways and processes in cells. It also uses electrolytic ion suppression, which enhances molecular specificity and selectivity.

In scientific studies, ion-exchange chromatography has been used since the 1970s, but researchers explain that it was challenging to couple it directly to mass spectrometry. However, the new technology overcomes this.

“Ion-exchange chromatography offers a retention and elution mechanism that is new to metabolomics and is proving to be a powerful solution for long-standing analytical challenges in the field,” says Rachel Williams, Ph.D. student in the McCullagh Group. This research group at the university explores molecular pathways and chemical mechanisms in biological systems.

Extreme levels of precision

The study notes that metabolomics is one of many omics technologies, which include genomics (mapping genomes) and proteomics (analyzing proteins), offering a “powerful combinatorial approach” to analyzing molecular systems.

Diseases, diets, nutritional states, treatments, and chemical exposures all cause changes in metabolite levels, which the new tool can detect. 

The researchers add that the tool can be applied to various fields, including biological chemistry, molecular biology, molecular medicine, pharmacology, and environmental science. “Robust, reproducible and quantitative methods for the analysis of highly polar and ionic metabolites help meet a longstanding analytical need in metabolomics,” the study details.

Professor James McCullagh with IC-MS.“The method requires minimal sample preparation and is robust, sensitive, and selective. It provides comprehensive coverage of hundreds of metabolites found in primary and secondary metabolic pathways.”

Proven in studies 

The AEC-MS technology has also been used in multiple research studies, including one that examined the gut microbiome to understand how it utilizes energy substrates. The study discovered that butyrate, the microbiome-derived energy substrate, helps to enhance immune responses.

Another study used AEC-MS to study metabolism in diabetic pancreatic β-cells. The researchers found that increased glucose inhibited enzymes (GAPDH and PDH), which are involved in the production of adenosine triphosphate (ATP) from glucose. This caused upstream intermediates to build up, causing changes in gene expression, insulin secretion, and glycogen buildup.

Project leader, professor James McCullagh at the Department of Chemistry at the University of Oxford, comments: “Developing a new metabolomics protocol is very exciting. It expands capability for existing applications but also enables us to explore and develop new applications.” 

“In our lab, we are now applying the protocol in several research areas, including investigating gut microbiome metabolism, how antimicrobial resistance impacts bacterial metabolism, and the discovery of biomarkers for the early detection of cancer.”

New technology for better science

Emerging technologies, such as AEC-MS, hold the potential to reduce reliance on animal testing by enabling more human-relevant science, which the Physicians Committee for Responsible Medicine flags as outdated. It told Nutrition Insight about the need for more training and expertise in such new methods among scientists and ethics review bodies. 

Calling out the tradition of animal tests, People for the Ethical Treatment of Animals (PETA) told us: “A successful path forward will involve the coordinated use of multiple models — in vitro human systems, computational biology, and other forms of human data. For complex studies, no one model will give the full picture, but a combination of human-based models will provide more useful data than an animal model ever could.” 

To support human and planetary health, the Innovation Institute for Food and Health at the University of California, Davis, US, combines several omics tests to map food components, holistically and synergistically tackling food analysis in multi-omics. These tests include data from different biological molecules of one specific type.