Harnessing the Metabolome

Spotting individual differences is the key to personalised medicine. In the future, identifying individuality using the metabolome – a personal metabolic snapshot at a particular instant – we may categorise patients into intervention responders and non-responders. By determining susceptibility to future disease and intervening early we may prevent disease from occurring.

We usually target specific metabolites when developing drugs. Using metabolomics offers a different approach as it generates a hypothesis, whereas we usually test a hypothesis. But once we generate the hypothesis it can then be tested.

Imaging technology – nuclear magnetic resonance or mass spectrometry – can generate unique signatures based on each individual’s environment and their genome at a particular time. These metabolomic signatures tend to cluster together – rats cluster with rats and humans with other humans. We, humans, eat different types of food and have different environments so we tend to have wider clusters than inbred rats that tend to have similar lifestyles.

By analysing different biofluids the aim is to look for the differences between for example disease and healthy individuals. For example using urine metabolic signatures a difference was found between osteoarthritis patients and controls, and between those with more severe and less severe disease.

In a study of cardiovascular disease, those with diseased arteries clustered in a signature different from those whose arteries were normal. In the future, metabolomic signatures may be more useful to traditional biomarkers such as cholesterol used to target patients for intervention. Perhaps it will help use blood and biofluid measurements in more informed way and predict outliers in disease and treatment response.

Interpreting data is complex and difficult. Signatures generate vast amounts of data and all of the metabolites in a pathway – some of them not yet identified. Looking at specific important molecules in a pathway simplifies the approach and helps separate signal from noise.

Examining the gut microflora offers an opportunity. We might identify specific microflora associated with gastrointestinal diseases, such as irritable bowel disease, and investigate how they affect metabolite profiles.

In population studies, it may be possible to investigate clusters of healthy people and diseased people with similar phenotypes to see if there are differences in their metabolome.

The way to harness the true potential of the metabolome is to predict healthy people who are likely to get ill and to intervene to protect them.



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