Twenty years of metabonomics: so what has metabonomics done for toxicology?

Abstract

In 1999 the journal Xenobiotica published a perspective article detailing the new concept of metabonomics and its application to toxicology. The approach was to apply analytical chemistry techniques, and in particular ¹H NMR spectroscopy, to profile biofluids and tissues to assess the metabolic effects of xenobiotics. Metabonomics has been shown to be sensitive not only to organ specific toxicity but also provides information on the cells, tissues and mechanisms involved, as well as their interactions with the host’s sex, age, diet and environment. This review assesses the impact of metabonomics on drug toxicology over the past twenty years and its future prospects. These applications include:

1. Pharmacometabonomics – the prediction of drug effects through the analysis of predose, biofluid metabolite profiles, which reflect both genetic and environmental influences on physiology.

2. The microbiomes role in toxicology – understanding how xenobiotics can be modified by the microbiome dramatically changing their impact on the host.

3. Development of expert systems for toxicity prediction.

4. Data fusion of different omics to better understand the underlying mechanisms of drug toxicity.

5. Metabonomics and exposome – understanding how multiple environmental toxicants might interact with the host organism to produce their overall phenotype. While there has been huge growth in the use of metabonomics within toxicology these applications are set to increase as the tools become more sensitive and robust, as well as the increased use of both experimental and in silico databases to aid prediction of toxicology.

Keywords:

• 1H NMR spectroscopy of biofluids
• mass spectrometry of biofluids
• metabolic profiling
• metabolomics
• multivariate statistics