The ability of metabolic ‘fingerprinting’ – examining the relative levels of different metabolites in human blood and urine – to identify the possible causes of serious disease in diet and lifestyle is borne out by the publication of the first ever metabolome-wide association study.

The metabolome is the sum collection of all the metabolites in a biological organism. In the study published in the latest issue of Nature, researchers from Imperial College London, Northwestern University in Chicago, Belgium’s Akademisch Ziekenhuis St. Rafael, Japan’s Shiga University of Medical Science and the Chinese Academy of Medical Sciences took urine samples from volunteers aged between 40 and 59 years and analysed them for more than several thousand metabolite signals using NMR (nuclear magnetic resonance) spectroscopy and advanced statistics.

The volunteers were taking part in INTERMAP, an epidemiological study investigating the links between diet and blood pressure. The metabolome study showed that people with increased levels of the amino acid alanine, which is present in a number of foods but especially prevalent in animal protein, have higher blood pressure as well as increased energy intake, levels of dietary cholesterol and body mass index.

People with higher levels of the metabolite formate also had increased energy intake but showed lower blood pressure. Formate arises from the action of microbes in the gut or as a product of metabolism in the body. Raised levels of hippurate, a by-product of microbe metabolism in the gut, were found in people with lower blood pressure, lower levels of alcohol intake and higher levels of dietary fibre.

More generally, the study demonstrated how lifestyle is a dominant feature in determining metabolism. Adults in the UK and the US, which have similar incidences of high blood pressure and cardiovascular disease, showed comparable metabolic fingerprints, reflecting similar lifestyles in spite of the geographical distance between the countries.

By contrast, and despite their similar genetic profiles, adults in Japan and China were found to have very different metabolic fingerprints from one another and from adults in the UK and US. There were also major differences between these countries in the incidence of many diseases. On the other hand, Japanese people in the US had metabolic fingerprints that resembled those of other US residents and differed from those of their counterparts in Japan.

“Metabolic profiling can tell us how specific aspects of a person’s diet can contribute to their risks for certain diseases, and these are things which we can’t investigate by looking at a person’s DNA,” commented Professor Jeremy Nicholson from Imperial College’s Department of Biomolecular Medicine, who was a co-author of the Nature paper. “What is really important is that we can test out our new hypotheses directly, in a way that is not easy with genetic biomarkers.”

Another co-author, Professor Paul Elliott from the college’s Department of Epidemiology and Public Health, added: “The flip-side of this is that whereas a person can’t alter their DNA, they can change their metabolic profile by changing their diet and lifestyle. This means that as we figure out where the problems lie, we should also be able to show people ways to reduce their risk of certain diseases.”