NMR-based pharmacometabonomics: A new paradigm for personalised or precision medicine

Abstract

Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systemsbased approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs. Differences in predose metabolite profiles between groups of subjects are used to predict postdose differences in response to drug administration. Thus the paradigm is inverted and pharmacometabonomics is the metabolic equivalent of pharmacogenomics. Although the field is still in its infancy, it is expected that pharmacometabonomics, alongside pharmacogenomics, will assist with the delivery of personalised or precision medicine to patients, which is a critical goal of 21 st century healthcare. Highlights metabonomics or metabolomics involves metabolic profiling by NMR or MS methods  metabonomics is used in a diagnostic mode to study the effects of an intervention  pharmacometabonomics is a prognostic method to predict the effects of drugs  pharmacometabonomics is a special case of predictive metabonomics  pharmacometabonomics will help to deliver personalised medicine in the future Graphical AbstractNMR-Based Pharmacometabonomics PNMRS 2017

Recent Advances in Targeted and Untargeted Metabolomics by NMR and MS/NMR Methods

“…Metabolites are direct read out of also non-sequence related influences on phenotypes, such as environmental perturbations; drought, temperature, light, and atmospheric CO 2 concentration [ 8 , 9 , 10 ]. The analysis of metabolite profiles of common biofluids, such as urine and serum, provides diagnostic and prognostic information about diseases, dietary patterns, and drug toxicity [ 11 , 12 , 13 ]. Stable isotope labeling of metabolites followed by the analysis of positional enrichments reveals activity of alternative metabolic pathways contributing to certain biochemical reactions, such as in healthy versus cancer cells [ 14 , 15 , 16 ].…”

A metabolic database for biomedical studies of biopsy specimens by high‐resolution magic angle spinning nuclear MR: a qualitative and quantitative tool

“…HRMAS NMR metabolomics has been shown to be potentially beneficial in personalized treatment in the following fields of medicine: Evaluation of the quality of grafts in liver or lung transplants Detection of oncometabolites for identification of DNA mutations: 2‐hydroxyglutarate in glioma for isocitrate dehydrogenase mutation, succinate in pheochromocytomas to distinguish succinate dehydrogenase (SDHx)‐ and non‐SDHx‐related tumors …”

Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives

“…Because it allows the discovery of biomarkers and the stratification of patients, metabolomics, as well as pharmacometabolomics which evaluates their response to treatment, are and will certainly be part, with genomics, transcriptomics and proteomics of the key tools in this new way of approaching pathologies ( Wishart, 2016 ; Jacob et al, 2019 ; Beger et al, 2020 ; Ashrafian et al, 2021 ). Its characteristics of reproducibility, robustness, speed and its ability to quantify metabolites, certainly position NMR as an analytical technique of choice in metabolomics-based personalized medicine, especially because longitudinal aspect is essential ( Everett, 2017 ; Jacob et al, 2019 ). As mentioned previously, clinical metabolomics and personalized medicine approach are clearly connected.…”