Das Food Metabolom als neues Konzept zur Erhebung der Ernährungsexposition bei Kindern
Epidemiologie und Medizinische Biometrie/Statistik
Zusammenfassung der Projektergebnisse
Objective dietary assessment is crucial to understand diet-disease associations; however, it is challenging in children to apply food related questionnaires. Biomarkers measured in urine may offer a complementary or alternate approach. The aim of the present project was to identify and validate biomarkers associated with dietary intake of children and adolescents in large European cohort studies. Therefore, the FOODMETCH project comprehensively studied the food metabolome as the totality of metabolites linked to diet. In total, 2400 urine samples that had been repeatedly collected from children and adolescents of the IDE- FICS/I.Family (morning urine samples) and DONALD cohort (24-h urine samples) were analyzed with untargeted metabolomics using high-resolution liquid chromatography-mass spectrometry from our collaboration partner at International Agency for Research on Cancer (IARC) Lyon. Untargeted metabolomics analysis yielded several thousand signals found in urine samples. These signals were further linked with dietary data from 24-h dietary recalls and food frequency questionnaire data (IDEFICS/IFamily), and 3-d weighted dietary records (DONALD cohort). Multivariate modelling with Unbiased Variable selection algorithms and linear mixed models were used to identify metabolites linked to acute and habitual food intake. In a second step, signals linked to diet were annotated. Reproducibility and sources of variation of food metabolites were studied using data from repeated sample collections. Finally, we assessed the association between dietary metabolites with measures of obesity and cardiometabolic risk using longitudinal cohort data. With this approach, potential biomarkers were identified and replicated for intake of sweet and fatty snacks, fruit and vegetables and sweetened beverages. Many of the mass spectrometry features that were linked to dietary intakes remained unknown; however, we provide their information in supplementary materials of the manuscripts for use in future studies. We identified three metabolites from caffeine metabolism linked to chocolate intake in children consistently in both cohorts. Their reproducibility in urine samples over two and four years ranged from intraclass correlation coefficients 0.23 to 0.55. Of them, xanthosine that was positively linked to chocolate intake was inversely associated with BMI z-score in the IDEFICS/I.Family study. For fruits and vegetables, ten metabolites were identified in IDEFICS/I.Family of which hippuric acid could also be identified and replicated in the DONALD cohort. Hippuric acid concentration was not associated with cardiometabolic risk markers. Other biomarkers of fruit and vegetable intake, such as ferulic acid 4-O-glucuronide and ferulic acid 4-O-sulfate that were found to be linked to orange intake in IDEFICS/I.Family were inversely associated with plasma glucose. Several metabolites of known and unknown identity for intake of sweetened beverages and total added sugars could be found in the DONALD cohort, such as urinary saccharine and acesulfame for low and no calorie sweetened beverages intake, and urinary sucrose for added sugar intake that were also positively associated to measures of adiposity. The FOODMETCH project was one of a kind. It combined explorative untargeted metabolomics with repeated data and biosamples from longitudinal cohort studies. Using cohorts of children was another unique strength of this project, as biomarkers of food intake had been understudied in children, where they would be very useful. With the approach of the FOODMETCH project, we confirmed that novel biomarkers can not only be found through experimental feeding studies, but also cost-efficiently through already existing biobanks in cohort studies. Future studies should focus on improvement of identification and annotation of mass spectrometry features from untargeted metabolomics, and in depth validate the potential biomarkers of food intake discovered in FOODMETCH.
Projektbezogene Publikationen (Auswahl)
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Omics Biomarkers in Obesity: Novel Etiological Insights and Targets for Precision Prevention. Current Obesity Reports, 9(3), 219-230.
Aleksandrova, Krasimira; Egea, Rodrigues Caue; Floegel, Anna & Ahrens, Wolfgang
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A review of the reliability of urinary biomarkers for environmental toxicant exposures. 16th annual meeting of the German Epidemiology Society (DGEpi), Würzburg 2021 (Talk)
Goerdten J., Yuan L., Huybrecht I., Nöthlings U., Ahrens W., Scalbert A. & Floegel A.
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A Systematic Review of Metabolomic Biomarkers for the Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages. Cluster Conference of the Competence Clusters Nutrition Research. Berlin/Virtual. May 17-19, 2021. (Poster)
Muli S., Goerdten J., Oluwagbemigun K., Floegel A., Schmid M. & Nöthlings U.
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A Systematic Review of Metabolomic Biomarkers for the Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages. Metabolites, 11(8), 546.
Muli, Samuel; Goerdten, Jantje; Oluwagbemigun, Kolade; Floegel, Anna; Schmid, Matthias & Nöthlings, Ute
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Exposure assessment in early life: it is about time for multi-omics approaches. BMC Medicine, 19(1).
Goerdten, Jantje & Floegel, Anna
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A systematic review of biomarkers of fruit and vegetables intake in children and adolescents. Presentation at 17th annual meeting of the German Epidemiology Society (DGEpi), Greifswald 2022 (winner of poster price)
Yuan L., Muli S., Huybrechts I., Nöthlings U., Ahrens W., Scalbert A. & Floegel A.
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Assessment of Fruit and Vegetables Intake with Biomarkers in Children and Adolescents and Their Level of Validation: A Systematic Review. Metabolites, 12(2), 126.
Yuan, Li; Muli, Samuel; Huybrechts, Inge; Nöthlings, Ute; Ahrens, Wolfgang; Scalbert, Augustin & Floegel, Anna
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Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis. Cancer Epidemiology, Biomarkers & Prevention, 31(9), 1683-1692.
Goerdten, Jantje; Yuan, Li; Huybrechts, Inge; Neveu, Vanessa; Nöthlings, Ute; Ahrens, Wolfgang; Scalbert, Augustin & Floegel, Anna
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The Exposome-Explorer database in 2022: recent developments on the gut microbial exposome and biomarker reproducibility. Presentation at Exposome-NL conference, Utrecht (Poster)
Neveu V., Nicolas G., Amara A., Goerdten J., Yuan L., Huybrechts I., Floegel A. & Scalbert A.
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Identification and replication of biomarkers for fruit and vegetable intake using untargeted metabolomics in European children cohorts. 61st scientific conference of the German Nutrition Society, Kassel 2024 (Poster)
Yuan L., Muli S., Goerdten J., Rattner J., Merdas M., Achaintre D., Foraita R., Wolters M., De Henauw S., Hunsberger M., Huybrechts I., Lissner L., Molnár D., Moreno L. A., Russo P., Veidebaum T., Nöthlings U., Ahrens W., Keski-Rahkonen P., Oluwagbemigun K. & Floegel A.
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Identification and replication of urine biomarkers of chocolate intake in European children and adolescents. 61st scientific conference of the German Nutrition Society, Kassel 2024 (Talk)
Goerdten J., Muli S., Rattner J., Merdas M., Achaintre D., Yuan L., De Henauw S., Foraita R., Hunsberger M., Huybrechts I., Lissner L,. Molnár D., Moreno L. A., Oluwagbemigun K., Russo P., Veidebaum T., Aleksandrova K., Nöthlings U., Keski-Rahkonen P. & Floegel A.
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Identification and Replication of Urine Metabolites Associated With Short-Term and Habitual Intake of Sweet and Fatty Snacks in European Children and Adolescents. The Journal of Nutrition, 154(11), 3274-3285.
Goerdten, Jantje; Muli, Samuel; Rattner, Jodi; Merdas, Mira; Achaintre, David; Yuan, Li; De Henauw, Stefaan; Foraita, Ronja; Hunsberger, Monica; Huybrechts, Inge; Lissner, Lauren; Molnár, Dénes; Moreno, Luis A.; Russo, Paola; Veidebaum, Toomas; Aleksandrova, Krasimira; Nöthlings, Ute; Oluwagbemigun, Kolade; Keski-Rahkonen, Pekka & Floegel, Anna
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Metabolomics signatures of sweetened beverages and added sugar are related to anthropometric measures of adiposity in young individuals: results from a cohort study. The American Journal of Clinical Nutrition, 120(4), 879-890.
Muli, Samuel; Schnermann, Maike E.; Merdas, Mira; Rattner, Jodi; Achaintre, David; Perrar, Ines; Goerdten, Jantje; Alexy, Ute; Scalbert, Augustin; Schmid, Matthias; Floegel, Anna; Keski-Rahkonen, Pekka; Oluwagbemigun, Kolade & Nöthlings, Ute
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“Introduction into the FOODMETCH project”. International workshop of the FOODMETCH project “Food metabolomics in children cohorts”, Virtual 2024 (Talk)
Floegel, A. & Noethlings U.
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“Metabolites of intake of fruit and vegetables and association with cardiometabolic risk markers in the IDEFICS/I.Family cohort”. International workshop of the FOODMETCH project “Food metabolomics in children cohorts”, Virtual 2024 (Talk)
Floegel A. & Yuan L.
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“Metabolites of intake of sweet and salty snacks, reproducibility and sources of variation in the IDEFICS/I.Family cohort.” International workshop of the FOODMETCH project “Food metabolomics in children cohorts”, Virtual 2024 (Talk)
Goerdten, Jantje
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“Metabolites of intake of sweetened beverages and ultra-processed foods and obesity risk in the DONALD cohort”. International workshop of the FOODMETCH project “Food metabolomics in children cohorts”, Virtual 2024 (Talk)
Muli S.
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“Untargeted Metabolomics platform at International Agency for Research on Cancer”. International workshop of the FOODMETCH project “Food metabolomics in children cohorts”, Virtual 2024 (Talk)
Keski-Rahkonen, P.
