UNDER EMBARGO UNTIL 10 AM BST / 5 AM ET FRIDAY 22 AUGUST 2025

Researchers develop an innovative method for large-scale analysis of metabolites in biological samples

More images available via the link in the notes section

Researchers from the McCullagh Group in Oxford University’s Department of Chemistry have published an innovative method in Nature Protocols today (22 August) that provides comprehensive analysis of metabolites found in cells, tissues and biofluids.

The new method delivers a step-change in capability for analysing highly polar and ionic metabolites. The innovation comes from using anion-exchange chromatography coupled to mass spectrometry (AEC-MS) to meet a long-standing need for improving the large-scale analysis of highly polar and ionic metabolites which drive primary metabolic pathways and processes in cells.

Ion-exchange chromatography has been used by generations of chemists since the 1970s, but historically it has been very difficult to couple directly to mass spectrometry, unlike other types of chromatography. The new method uses electrolytic ion-suppression which links the high-performance ion-exchange chromatography system directly with mass spectrometry, an innovation that improves molecular specificity and selectivity. This has led to new applications that were recently reviewed by the McCullagh Group (Ngere et al., Anal. Chem., 2023). The new method is designed for metabolomics applications which involve the large-scale analysis of metabolites in biological samples.

Rachel Williams, a D.Phil. student in the McCullagh Group, whose research focusses on the development of ion-exchange chromatography-mass spectrometry, said, “Ion-exchange chromatography offers a retention and elution mechanism which is new to metabolomics and is proving to be a powerful solution for long-standing analytical challenges in the field.”

Metabolomics, is one of several ‘omics’ technologies, that include genomics and proteomics, offering a powerful combinatorial approach to comprehensively analyse molecular systems in cells, tissues and whole organisms. Changes in metabolite levels are sensitive biomarkers for specific diseases, diets, nutritional states, treatments and chemical exposures and metabolomics provides a tool for discovering these molecular changes. It can be applied to research questions in many disciplines, including biological chemistry, molecular biology, molecular medicine, pharmacology and environmental science.

The new AEC-MS protocol has been used in several research studies including in collaboration with the Kennedy Institute, Oxford to investigate how the gut microbiome utilises energy substrates. This led to the discovery that the microbiome-derived energy substrate product butyrate is found in circulation and can help bolster the host immune response (Schulthess et al., Immunity, 2019).

In another study it was used to investigate metabolism in diabetic pancreatic β-cells. We found the activity of GAPDH and PDH (enzymes involved in the production of ATP from glucose) were inhibited when glucose levels increased, leading to the accumulation of upstream intermediates which caused changes in gene expression including impaired insulin secretion and build-up of glycogen (Haythorne et al., Nat. Comms., 2023).

Professor James McCullagh (Department of Chemistry, University of Oxford) who led the project, said: “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 in the discovery of biomarkers for the early detection of cancer.”

Notes to editors:

For media enquiries, contact Susan Davis or Thomas Player, Department of Chemistry, University of Oxford (chemistry-news@chem.ox.ac.uk) or Professor James McCullagh (james.mccullagh@chem.ox.ac.uk)

The study ‘Metabolomics using anion-exchange chromatography mass spectrometry for the analysis of cells, tissues and biofluids’ will be published in Nature Protocols at 10 am BST / 5 am ET Friday 22 August 2025 at: https://doi.org/10.1038/s41596-025-01222-z. To view a copy of the paper before this under embargo, contact Professor James McCullagh (james.mccullagh@chem.ox.ac.uk).

Images related to the study that can be used to illustrate articles can be found here https://drive.google.com/drive/folders/1RNPNVg5tOusE5yOyGde2el55RJ9XDJFx?usp=sharing These are for editorial purposes related to this press release ONLY and MUST be credited to Isabelle Legge. They MUST NOT be sold on to third parties.

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