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Finding Signs in Metabolites

An international study has found that urine can offer an in-depth snapshot of what’s going on inside a person’s body. The results revealed differences between populations and uncovered relationships between several urine components and blood pressure.

Genomics—the study of all the genes in an organism—has driven many of the advances in medical research over the past few years. Proteomics—the study of all the proteins in an organism—has also been making news. Metabolomics goes a step further, capturing snapshots of the body’s physiological state at a given point in time. Metabolomics focuses on the products of chemical reactions throughout the body, called metabolites. These encompass carbohydrates, lipids and other molecules produced by our bodies. They also come from microbes living in our bodies and the things we eat and breathe.

An international research team led by Dr. Jeremy K. Nicholson and Dr. Paul Elliott of Imperial College London analyzed metabolites in urine to try to gain insight into high blood pressure and related disorders. The group was supported by NIH’s National Heart, Lung and Blood Institute (NHLBI); the Chicago Health Research Foundation; and national agencies in Japan, China and the UK. The researchers used NMR spectroscopy to analyze urine specimens from 4,630 participants, aged 40–59, from China, Japan, UK and USA. This technique can detect a wide variety of metabolites, generating graphs with thousands of peaks representing different compounds.

The team reported online on April 20, 2008, in the journal Nature that East Asian and western populations have different metabolic profiles. Differences between people from different geographic regions proved to be greater than those between genders. The profiles of southern (Guangxi) and northern (Beijing and Shanxi) Chinese are also different from each other, whereas those of the UK and USA population samples overlap. The profiles showed differences between people based on their diets as well—for example, distinguishing between people living in Japan and Japanese-Americans.

The group was able to uncover relationships between several specific metabolites and blood pressure. Higher alanine levels were associated with higher blood pressure. Hippurate and formate levels, in contrast, had an inverse association with blood pressure. The researchers found that formate and sodium levels in urine were also linked. Given the importance of sodium in blood pressure control, this result suggests a possible new role for formate in blood pressure regulation.

This study is the one of the largest to examine links between metabolomics and cardiovascular disease risk factors. The associations it uncovered can now be tested in follow-up studies.

Metabolomics may one day prove useful in the clinic as well, helping doctors diagnose disease and assess someone’s risk of trouble in the future. “Whereas a person can't alter their DNA, they can change their metabolic profile by changing their diet and lifestyle,” Elliott explained. “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.”

—by Harrison Wein, Ph.D