Pharmacometabonomics as an Effector for Personalized Medicine

Abstract

This article introduces and reviews the concept of pharmacometabonomics, with recent experimental exemplifications of the approach being described and discussed. Pharmacometabonomics seeks to predict the response of an individual to a stimulus (e.g., drug, toxin, surgery, nutrition and so on) prior to the stimulus or other perturbation. It is an integral part of top-down systems biology which aims to improve understanding of phenotypic differences and the impact of beneficial and pathological interventions. The pharmacometabonomic concept is also integral to the understanding of mammalian-gut microbiome cometabolic interactions and their consequences, including the impact on disease and therapy. Although the subject is only at an early stage and requires further exemplification and validation, the approach has major implications for improved efficiency in drug discovery efforts, for example, by enabling more careful selection of animals in preclinical studies, for better stratification of patients in drug clinical trials and for individualized therapies. It could also find application in population-wide large cohort studies and in studies of nutrition where it would allow the elucidation of health risk factors and provide easily measured surrogate biomarkers.

KEYWORDS::

• animal models
• disease
• gut microflora
• mass spectrometry
• metabolomics
• metabonomics
• nuclear magnetic resonance
• pharmaceuticals
• pharmacometabonomics
• therapy

Acknowledgements

The authors thank our collaborators in the development and exemplification of pharmacometabonics, particularly Dr Andy Clayton who carried out many of the metabonomic studies that are reviewed here, and Dr Jeremy Everett from Pfizer Global R&D who codirected that project and who originally helped coin the term metabonomics.

Author disclosure

All authors had equal input and all wrote the manuscript.

Financial & competing interests

Jeremy K Nicholson and John C Lindon are founders, minority stockholders and directors of a company, Metabometrix Ltd, that undertakes commercial studies in the field of this article. Ian D Wilson is an employee of a commercial company with an interest in conducting metabonomics studies. Jeremy K Nicholson and John C Lindon are named inventors on a patent filing relating to pharmacometabonomics. We thank Pfizer for providing financial support to Dr TA Clayton (Imperial College London, UK) who carried out our research that is reviewd here. This is an article based largely on published work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Jeremy K Nicholson and John C Lindon are founders, minority stockholders and directors of a company, Metabometrix Ltd, that undertakes commercial studies in the field of this article. Ian D Wilson is an employee of a commercial company with an interest in conducting metabonomics studies. Jeremy K Nicholson and John C Lindon are named inventors on a patent filing relating to pharmacometabonomics. We thank Pfizer for providing financial support to Dr TA Clayton (Imperial College London, UK) who carried out our research that is reviewd here. This is an article based largely on published work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.