Integration of LC–MS-based untargeted and targeted metabolomics to uncover novel whole-grain wheat dietary intake biomarkers in the plasma of the Chinese population

• Published in: Food research international Vol. 202; p. 115740
• Main Authors: Yang, Yunjia, Zhou, Yalin, Ye, Wanyun, Shi, Hanxu, Wen, Zhang, Peng, Yile, Han, Muke, Shao, Bing, Xu, Yajun
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.02.2025
• Subjects: Adult; Asian People; Biomarker; biomarkers; Biomarkers - blood; China; Chromatography, Liquid - methods; clinical trials; compliance; Cross-Over Studies; Diet; dose response; East Asian People; Female; food intake; food research; Humans; ingestion; Liquid Chromatography-Mass Spectrometry; Male; metabolism; metabolites; Metabolomics; Metabolomics - methods; Middle Aged; nutritional intervention; oxidation; Phytochemical; quantitative analysis; refined grains; Resorcinols - blood; sulfates; Tandem Mass Spectrometry - methods; Triticum - metabolism; wheat; whole grain foods; Whole grains; Whole Grains - metabolism; Young Adult; China; Metabolomics; Biomarker; Whole grains; Phytochemical
• ISSN: 0963-9969; 1873-7145; 1873-7145
• DOI: 10.1016/j.foodres.2025.115740

[Display omitted] •The first dietary intervention study to identify WG BFIs in the Chinese population.•AR-OOH-sul were firstly identified as novel short-term WG Plasma BFIs.•AR-glu is considered a promising medium- and long-term WG BFIs.•Predictive ability and dose–response of BFIs was validated in an independent study.•New insights into the metabolism of WGs across genetic origins and dietary cultures. Biomarkers of food intake (BFIs) for whole grains (WGs) would enable more precise dietary assessments and help investigate WG’s health effects. However, no reports have been published on the biomarkers that reflect the intake of WG wheat in the Chinese diet. In an acute, randomized, crossover intervention study performed on 22 Chinese subjects, WG wheat BFI candidates were screened using an LC-HRMS untargeted metabolomics technique. Screening results indicate that alkylresorcinol (AR) metabolites are WG wheat-specific metabolites. These metabolites were systematically characterized by in vitro metabolism reaction, and the matched high-throughput LC–MS/MS-targeted quantitative method was developed. Time-response plots generated via targeted analysis revealed AR oxidation products (AR-OOH) and their sulfate conjugates (AR-OOH-sul) increased rapidly following the WG wheat consumption, which were identified as novel and short-term WG wheat BFIs. Another attractive biomarker was glucuronidated ARs (AR-glu), which can distinguish between WG and refined grain (RG) groups 24 h after WG wheat ingestion and is considered a promising medium- and long-term biomarker. Subsequently an independent dose–response study was performed for 38 volunteers who consumed different WG wheat amounts (0, 25, 50 or 100 g) for further validation. Identified BFIs perform well in classifying participants into WG wheat consumers or non-consumers, and could capture dose-dependent changes with WG intake increased. Overall, this is the first study to discover and validate WG BFIs in the Chinese population via dietary intervention trials, indicating the potential usefulness for WG wheat intake assessments and dietary compliance monitoring. Future work will examine their use in large-scale free-living populations.