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An Italian and German research team has used NMR spectroscopy to fingerprint a person's metabolic phenotype. Their work shows that while the range of metabolic products and their concentrations varies significantly from person to person they are relatively stable over time for each individual. For decades, the word "fingerprints" has been used to denote a set of unique characteristics, whether literally the complex patterns of arches, loops, and whorls on one's fingertips or entirely figuratively and more recently, the notion of a genetic fingerprint based on an analysis of an individual's DNA sequence. Now, NMR spectroscopy has revealed that an "omic" other than genomic could provide a unique view of each of the 6.7 billion people on earth - their metabonomic fingerprint. Metabolism is an incredible milieu of biochemical reactions, many enzymically driven others pursuing radical chain reactions, others behaving almost identically in vivo as do in vitro processes. Ultimately, the body uses metabolism to convert food into energy, to grow, to repair damage from disease and injury, and for reproductive processes. Metabolism is also the route by which ingested non-foods, such as toxic compounds and medicines are converted into active or deactivated forms. It would seem unlikely that any two individual metabolic profiles would be exactly the same. Now, Patrizia Bernini, Ivano Bertini, Claudio Luchinat, Stefano Nepi, Edoardo Saccenti, and Leonardo Tenori of the Magnetic Resonance Center (CERM), at the University of Florence, and the FiorGen Foundation, working with Hartmut Schfer, Birk Schuetz, and Manfred Spraul of Bruker BioSpin GmbH, discuss new evidence that this is indeed the case. At the fundamental level individuals are different in many ways, our metabonome is almost inevitably going to be unique because we each have a unique genome producing a unique set of proteins, our phenotype, and our exposure to different environmental factors, food, air, and water etc are unique to each of us too. "A fundamental contribution to the definition of the individual phenotype for clinical and therapeutic applications would come from a deeper understanding of the metabolic phenotype," the researchers explain. It is to this important end that they have investigated the details of the individual metabolic phenotype and have finally obtained experimental evidence to support the hypothesis that such a unique biochemical profile exists for each of us. For a metabonomic fingerprint to be of use medically, and perhaps forensically, then variation on the timescale of years would also have to be shown to be relatively invariant if peaks and troughs in particular metabolites are to be useful for any kind of diagnosis. Moreover, if doctors are now dreaming of truly personalised medicine, pharmacogenomics, then they need at their disposal tests that can not only diagnose a disease in its earliest stages, but also match up the individual's metabonomic fingerprint for specific drugs that will actually work with minimal side-effects. Such an approach would contrast starkly and hopefully beneficially with the current one-size-fits all medicine. If each of our metabonomic fingerprints proves reliably stable throughout our lives except during periods of illness or on exposure to particular toxic compounds, then this personalised approach to treatment might ultimately become a reality. Bertini and colleagues have used 600 MHz 1D 1H NMR spectroscopy to analyse more than 1849 urine samples from thirty-one people who were monitored for two to three years. The researchers were able to identify individual patients from their metabolic profiles with almost 100% accuracy consistently over the experimental timescale. They also found that the metabonomic profile is strongly affected by both gut microbiome and the person's metabolic phenotype, which is defined by genetic and environmental contributions. In other words, the microbial flora and fauna that reside in your intestines have a role to play in making you unique too. "Analysis of individual phenotypes over the timescale of years demonstrates that metabolic phenotypes are the results of complex interaction between environmental factors and genetics," the researchers explain. "The effects of the environment are observable in the periodical and/or sporadic metabolic fluctuations, while a combination of genetic and environmental contributions is present in the stable, invariant part of the metabolic phenotype that allows us to recognize spectra as belonging to a unique subject even over a period of some years."
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.jpg) NMR taking internal fingerprints |
