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NMR Study Recognizes Individual Metabolic Phenotypes

NEW YORK (GenomeWeb News) – An Italian and German research team has found evidence suggesting individual metabolic phenotypes differ from one individual to the next but are actually quite stable within each individual over time — a finding that they say might eventually open the door for personalized medical treatments based on metabolic profiling.

The researchers used nuclear magnetic resonance spectroscopy to profile metabolites in more than 1,800 urine samples collected from the same individuals for up to three years to test whether metabolic phenotype varies between different people at different times. The research, which appeared online recently in the Journal of Proteome Research, supports the notion that metabolic profiles are relatively stable within the same individual over time but vary between individuals.

"[I]ndividual metabolic phenotypes describe the fact that each individual possesses a unique adaptive response to the environment," corresponding author Ivano Bertini, director of the Center of Magnetic Resonance at the University of Florence, and his colleagues wrote.

"The present work … strongly supports the idea that the individual metabolic phenotype can also be considered a metagenomic entity that links gut microbiome and host metabolic phenotype; that is, the composition of the gut microflora is compatible with the genome of the host," they added.

Human metabolism encompasses a diverse range of chemical processes that go on in an individual's body. Being able to characterize and distinguish between individuals based on their metabolic profiles may eventually offer an avenue for customizing medications and treatments based on metabolism, the researchers noted. But so far that has been difficult to determine, since metabolic profiles — as gauged by NMR spectra of urine samples — can vary from day to day.

"For an individual metabolic phenotype to be of physiological relevance and medical usefulness, one should now be able to show that it is relatively stable over time for a period of at least a few years and, above all, what are the most relevant causes of its variability, if any, and their relative weight with respect to a possible invariant contribution of genetic origin," the authors explained.

To test this, the researchers assessed metabolic profiles for a total of 31 healthy individuals between the ages of 25 and 55 years old, collecting 40 urine samples from each over about three months. Eleven individuals provided two 40-sample sets over two years and four individuals provided three sets over three years. They then analyzed each urine sample using Bruker 600 MHz or 900 MHz NMR spectroscopy to get 1D and, in some cases, 2D spectra.

The team also collected information on everything from the participants' gender and age to their physical activity, diet, and body mass index.

Using this approach, the team found that the set of metabolites in each person's urine did not seem to change dramatically with time or the subject's age. Even so, the researchers did detect what they called "sporadic metabolic fluctuations" — including patterns classified as "spikes," "jumps," and "waves" in metabolite patterns. The team attributed such vacillations to environmental effects such as diet, physical activity, and gut microbes.

Nevertheless, the authors noted, "inter-individual discrimination [of metabolic phenotype] is still possible and very strong." When they randomly picked out different spectra, the researchers reported a 99.5 percent recognition rate, on average. The recognition rate decreased slightly over two or three years, the team found, but was still more than 97 percent over two years and above 92.5 percent after three years.

And while the team noted that more research must be done to predict how many metabotypes might exist in humans, they speculated that it is on the order of more than a few tens of different types.

Although they did not collect genetic information on the research participants, the researchers did note that more closely related individuals had more similar metabolic phenotypes in their study — hinting at a genetic component to metabotype.

Overall, the researchers concluded, "individual metabolic phenotype can also be considered a metagenomic entity that is strongly affected by both gut microbiome and host metabolic phenotype, the latter defined by both genetic and environmental contributions."

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