Discovery and validation of urinary exposure markers for different plant foods by untargeted metabolomics

Abstract

While metabolomics is increasingly used to investigate the food metabolome and identify new markers of food exposure, limited attention has been given to the validation of such markers. The main objectives of the present study were to (1) discover potential food exposure markers (PEMs) for a range of plant foods in a study setting with a mixed dietary background and (2) validate PEMs found in a previous meal study. Three-day weighed dietary records and 24-h urine samples were collected three times during a 6-month parallel intervention study from 107 subjects randomized to two distinct dietary patterns. An untargeted UPLC-qTOF-MS metabolomics analysis was performed on the urine samples, and all features detected underwent strict data analyses, including an iterative paired t test and sensitivity and specificity analyses for foods. A total of 22 unique PEMs were identified that covered 7 out of 40 investigated food groups (strawberry, cabbages, beetroot, walnut, citrus, green beans and chocolate). The PEMs reflected foods with a distinct composition rather than foods eaten more frequently or in larger amounts. We found that 23 % of the PEMs found in a previous meal study were also valid in the present intervention study. The study demonstrates that it is possible to discover and validate PEMs for several foods and food classes in an intervention study with a mixed dietary background, despite the large variability in such a dataset. Final validation of PEMs for intake of foods should be performed by quantitative analysis.

The role of metabolomics in determination of new dietary biomarkers

“…This approach has resulted in the identification of a number of putative biomarkers of specific foods and drinks such as citrus fruit (49,51,52) , cruciferous vegetables (53,54) , red meat (55,56) , coffee (57,58) , tea (59,60) , sugar-sweetened beverages (61) and wine (62) . A good example of a robust biomarker of citrus fruit is proline betaine, which was identified initially by Atkinson et al (52) and subsequently validated by independent research groups (49,51,63) . The biofluid used in all of these studies was urine; however, different metabolomic analytical strategies were applied to measure proline betaine, which included NMR and MS. One such study was performed by Heinzmann et al (49) , which involved eight volunteers consuming standardised meals over a 3 d period.…”

Metabolomics as a tool in the identification of dietary biomarkers

“…A number of research groups have also used dietary interventions to investigate biomarkers of cruciferous vegetables (25)(26)(27) . Andersen et al performed a controlled crossover meal study with nine brassica-containing New Nordic Diet meals in seventeen subjects (26) .…”

“…Further biomarkers of other foods, including fish were also identified (26) . To validate the biomarkers from this study, Andersen et al (27) carried out a 6-month parallel dietary intervention study where 107 participants were randomised (58) into two distinct dietary patterns. Combining liquid chromatography-MS data from 24 h urine samples and data from 3-d weighed dietary data the present study again identified conjugates of isothiocyanates as brassica biomarkers.…”

“…However, using this approach it was only possible to verify 23 % of potential biomarkers observed in the previous-meal studies (27) . As this was a less controlled intervention that included a wider selection of foods with varied amounts of intake and different preparation methods, it highlights the need for the validation of biomarkers in different subjects and study settings (27) . A number of red meat and fish biomarkers have been identified using this intervention approach (7,28,29) .…”

Exploring the Links between Diet and Health in an Irish Cohort: A Lipidomic Approach

“…6,8 The third approach looks at the concept of using biomarkers to reflect dietary patterns, where profiles have been linked to habitual dietary patterns to identify nutritypes and biomarkers. [9][10][11][12] These approaches have led to the identification of a number of putative biomarkers of exposure to certain foods and beverages such as red meat, 13,14 citrus fruits, [15][16][17] cruciferous vegetables, 18,19 coffee 20,21 and sugar sweetened beverages. 8 Examples of such biomarkers include proline betaine which has been associated with citrus fruit intake in a range of different studies.…”