Urinary metabolic ‘signatures’ predict diet quality and metabolic health in European children

An international research team has identified metabolic ‘signatures’ in urine that can determine the quality of diets in children across Europe and predict their metabolic health. 

Their methods, described today in eLife, could be used in addition to traditional questionnaires to objectively assess dietary patterns in children, and in future studies to evaluate the quality of participants’ diets. This knowledge can provide further insights on shared biological pathways that characterise healthy and unhealthy dietary patterns, as well as diet-related metabolic changes associated with diseases such as diabetes.

While previous research has identified diet-related changes in people, these studies have focused largely on selected food groups including fruit, vegetables, meat and seafood. On the other hand, dietary patterns related to the consumption of ultra-processed foods, which are high in sugars and fat, have been studied much less, despite more of this food being consumed across the globe.

“The objective assessment of dietary habits is important for the prevention of chronic diseases. Public health organisations typically base their recommendations on research on dietary habits,” says Alexandros Siskos, Research Associate at Imperial College London, UK. Siskos is a co-first author of the study alongside Nikos Stratakis (ISGlobal, Barcelona), and Eleni Papadopoulou (Norwegian Institute of Public Health, Oslo, Norway). 

“Urinary metabolic profiling is a promising, powerful tool for assessing food intake and can help us understand metabolic alterations in people in response to their diet quality,” adds Nikos Stratakis, who was a Postdoctoral Researcher at Keck School of Medicine of USC, Los Angeles, US, at the time the study was carried out, and is now a Postdoctoral Fellow at ISGlobal. “We set out to develop a way to identify urinary metabolites associated with a Mediterranean diet or the consumption of ultra-processed foods in European children and to determine the extent to which these metabolites might be able to predict disease risk.” 

The team’s multi-country study is embedded within the Human Early-Life Exposome (HELIX) project – a collaborative project that includes six population-based birth cohort studies in Europe, from the UK, France, Lithuania, Spain, Norway and Greece. The population for the current study consisted of 1,147 children from the project with available information on dietary intake, C-peptide levels in their blood plasma, and metabolomic biomarkers in their urine collected during a HELIX follow-up at a mean age of almost eight years old.

The researchers applied a technique called nuclear magnetic resonance (NMR) spectroscopy to profile the urinary metabolites from this population. Their work revealed a common panel of four metabolites – hippurate, N-methylnicotinic acid, urea and sucrose – that indicated whether a child followed a Mediterranean diet or consumed more ultra-processed foods. Children who adhered to a Mediterranean diet had higher levels of hippurate, N-methylnicotinic acid and urea, along with lower levels of sucrose, or sugar. On the other hand, those who consumed more ultra-processed foods had lower levels of hippurate, N-methylnicotinic acid and urea, and higher levels of sugar.

The team then studied the extent to which these metabolites were associated with C-peptide, a substance used as an early indicator of metabolic disease risk. For each cohort, the researchers assessed the concentration of C-peptide in the blood plasma samples. They found that higher adherence to a Mediterranean diet was associated with lower C-peptide levels, while the opposite was seen for those who consumed more ultra-processed foods.

The findings of this study come with a few limitations, including around the use of NMR spectroscopy for urinary metabolite profiling. While this technique allowed the team to clearly identify and profile metabolites, it limited the number of metabolites they were able to measure across entire urine samples. “Our work should be supplemented with other complementary metabolomic approaches in future, such as mass spectrometry,” says co-senior author Hector Keun, Professor of Biochemistry at Imperial College London. “This would help to enhance the identification and quantification of urinary metabolites associated with diet quality in children.”

“Further studies examining the association of diet quality and related metabolomic profiles with C-peptide will also be needed to replicate our findings,” adds co-senior author Leda Chatzi, Professor of Population and Public Health Sciences at Keck School of Medicine of USC. “For now, our work provides further evidence to support efforts by public health authorities to recommend increased adherence to a Mediterranean diet. Limiting the consumption of ultra-processed foods in childhood could lower the risk of disease later on.”

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This study was funded by the European Union and the National Institute of Environmental Health Sciences, US.

For more information about the HELIX project, visit https://www.projecthelix.eu.

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