Scientists at Imperial College London report on the development of a new type of rapid urine test that measures the health of a person’s diet, and produces an individual’s unique urine “fingerprint.” The researchers, working in collaboration with colleagues at Northwestern University, University of Illinois, and Murdoch University, analyzed levels of different metabolites in the urine of more than 1,500 people in the United States. Their results, published in Nature Food (“Nutriome-metabolome relationships provide insights into dietary intake and metabolism”), uncovered a link between dozens of metabolites in urine, and types of food or nutrients in the diet. Metabolites produced as different foods are digested are considered to be an objective indicator of diet quality.

In a second paper, also published in Nature Food (“Dietary metabotype modeling predicts individual responses to dietary interventions”), the Imperial researchers, in collaboration with colleagues at Newcastle University, Aberystwyth University, and Murdoch University, used the technology to develop a five-minute urine test. Their results of initial testing showed that the mix of metabolites in urine varies from person to person, even when they eat the same diet.

The team said the technology could help health professionals to tailor healthy eating advice —“precision nutrition”—to people, based on the quality of their diet and individual biological make-up. Joram Posma, PhD, lecturer in cancer informatics, at Imperial’s department of metabolism, digestion and reproduction, is first author of the “Nutriome-metabolome relationships provide insights into dietary intake and metabolism” paper. He said, “Diet is a key contributor to human health and disease, though it is notoriously difficult to measure accurately because it relies on an individual’s ability to recall what and how much they ate. For instance, asking people to track their diets through apps or diaries can often lead to inaccurate reports about what they really eat. This research reveals this technology can help provide in-depth information on the quality of a person’s diet, and whether it is the right type of diet for their individual biological make-up.”

Although poor diet is a major contributor to chronic disease, it is extremely challenging to obtain accurate data on dietary patterns and intake, the authors wrote. “Traditional methods rely on self-reports, which are prone to misreporting and bias, potentially resulting in erroneous associations between diet and disease risk.” New approaches are needed to help understand the metabolic consequences of dietary intakes, eating patterns, and their relation to disease risk.

The Imperial College London researchers, together with their collaborators, used 1H NMR spectroscopy to analyze levels of metabolites in the urine of 1,848 people in the International Population study on Macronutrients and Blood Pressure (INTERMAP) cohort. Their results revealed an association between 46 metabolites in urine, and different types of foods or nutrients in the diet. “… we measured a diverse set of urinary metabolites (the functional nutriome) with implications for understanding pathways leading from dietary intakes to disease,” the team commented.

For instance, certain metabolites correlated with alcohol intake, while others were linked to intake of citrus fruit, fructose (fruit sugar), glucose, and vitamin C. The investigators also found metabolites in urine that were associated with dietary intake of red meats, other meats such as chicken, and nutrients such as calcium. In addition, the results indicated that certain metabolites were linked with health conditions. For example, compounds such as formate and sodium (an indicator of salt intake) found in urine are linked with obesity and high blood pressure.

The team said that in contrast with other approaches for dietary analysis, their urinary spectroscopic characterization objectively captured the end products of metabolism so as to overcome the problems of reporting bias in dietary records. It also takes just five minutes to obtain an 1H NMR spectrum containing hundreds of metabolites measured simultaneously, which means the approach is scalable.

Paul Elliott, PhD, study co-author and chair in epidemiology and public health medicine at Imperial, noted, “Through careful measurement of people’s diets and collection of their urine excreted over two 24-hour periods we were able to establish links between dietary inputs and urinary output of metabolites that may help improve understanding of how our diets affect health. Healthful diets have a different pattern of metabolites in the urine than those associated with worse health outcomes.”

“We propose that the metabolome can be used as a proxy measurement to understand functional relationships between nutrients and health outcomes,” the authors commented. “Our findings suggest that the urinary metabolic profile has utility as an objective measure to classify people based on their adherence to healthy dietary patterns in free-living populations.”

They concluded, “These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers is associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to an unhealthy metabolic phenotype and hence indicate entry points for prevention and intervention strategies.”

In the second study, also recently published in Nature Food, the same Imperial team, working with colleagues in the U.K. and Australia, used their technology to develop a five-minute test that can reveal interindividual differences in urinary metabolites, and so generate what they call a dietary metabotype score for each individual. “In this feasibility study, we create an individual Dietary Metabotype Score (DMS) that embodies interindividual variability in dietary response and captures consequent dynamic changes in concentrations of urinary metabolites,” they explained.

For their experiments, the team asked 19 people to follow four different diets—ranging from very healthy (following 100% of World Health Organisation recommendations for a balanced diet), to unhealthy (following 25% WHO diet recommendations). They found that people who strictly followed the same diet had varied DMS scores.

The team’s work also revealed that the higher a person’s DMS score, the healthier their diet. A higher DMS score was also found to be associated with lower blood sugar, and a higher amount of energy excreted from the body in urine. “In this feasibility study, we have found that among a ‘healthy’ group of subjects, the participants who have a higher loss of energy in the urine (that is, those that also are at the top of the dietary metabotype score ranking) demonstrate greater urinary excretion of microbial metabolites,” the investigators wrote.

The results indicated that the difference between high energy urine (i.e., high DMS score) and low energy urine (low DMS score) was equivalent to someone with a high DMS score losing an extra four calories a day, or 1,500 calories a year. The investigators calculated that this could translate to a difference of 215 g of body fat per year. “Thus, this apparently small change over time becomes clinically important,” they stated.

“In summary, our feasibility study demonstrates that there are interindividual differences in response to the same diet, even when the environment is controlled. We have developed a modeling framework that could be used to monitor individual response to diet and that provides a mechanism for enhancing dietary advice with the potential to inform decision-making strategies for the prevention, risk reduction, and clinical management of NCDs [non-communicable diseases] for precision medicine.”

The next step may be to investigate how a person’s urine metabolite fingerprint may link to a person’s risk of conditions such as obesity, diabetes, and high blood pressure. “These findings bring a new and more in-depth understanding of how our bodies process and use food at the molecular level,” commented Gary Frost, PhD, co-corresponding author, and chair in nutrition and dietetics at Imperial. “The research brings into question whether we should re-write food tables to incorporate these new metabolites that have biological effects in the body.”

Co-author John Mathers, PhD, director of the Human Nutrition Research Centre at Newcastle University, added, “We show here how different people metabolize the same foods in highly individual ways. This has implications for understanding the development of nutrition-related diseases and for more personalized dietary advice to improve public health.”

First author Isabel Garcia-Perez, PhD, lecturer in precision & systems medicine, at Imperial’s department of metabolism, digestion and reproduction further said, “Our technology can provide crucial insights into how foods are processed by individuals in different ways—and can help health professionals such as dieticians provide dietary advice tailored to individual patients.” Garcia-Perez indicated that the team now plans to use the diet analysis technology on people at risk of cardiovascular disease.

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