Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches.

Yingdong Zhu,Wei Sha,Shengmin Sang,Pei Wang

doi:10.1038/srep36278

Abstract

Mounting evidence suggests that whole grain (WG) intake plays an important role in chronic disease prevention. However, numerous human studies have failed to produce clear-cut conclusions on this topic. Here, a combination of non-targeted and targeted metabolomics approaches, together with kinetic studies, was used to investigate biomarkers of WG wheat intake and further explore the diet-disease associations. Via these integrated approaches, forty-one compounds were identified as the most discriminating endogenous metabolites after WG versus refined grain (RG) wheat bread consumption. The corresponding biological assessment of these endogenous changes suggests that, in contrast to RG consumption, WG wheat consumption may facilitate antioxidant defense systems and moderate the risk factors of cancer, cardiovascular diseases, and other chronic diseases. A panel of urinary markers consisting of seven alkylresorcinol metabolites and five benzoxazinoid derivatives as specific biomarkers, as well as five phenolic acid derivatives, was also established to cover multiple time points and longer time periods for correctly and objectively monitoring WG wheat intake. Through these findings, we have established a comprehensive biomarker pool to better assess WG wheat consumption, and to monitor the endogenous changes that are linked to health effects of WG wheat consumption.

Highlights

Metabolomics is the comprehensive analysis of all metabolites in a biological system1, and has been applied in various areas to quantitatively assess biochemical fluxes and metabolites that are indicative of unusual biological or environmental perturbations2
To verify the validity of the separation at each interval between the Whole grains (WG) and refined grains (RG) groups, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) was further performed at each interval separately, and permutation-based validation was used to determine if the separation was statistically valid
The results from the three analyses suggest that there was some overall difference between WG and RG samples when all of the time points were considered, but a statistically significant difference was only observed at 2–4 h and 4–6 h after the WG or RG consumption

Summary

Introduction

Metabolomics is the comprehensive analysis of all metabolites in a biological system, and has been applied in various areas to quantitatively assess biochemical fluxes and metabolites that are indicative of unusual biological or environmental perturbations. There are limitations for ARs, BXs, or their metabolites when as single use exposure biomarkers of WG wheat and rye intake in cohort studies. A non-targeted metabolomics approach was applied to analyze all metabolites, including dietary exposures and endogenous biomarkers, in urine samples collected from WG wheat bread- and RG wheat bread-consumers, and a targeted metabolomics approach was utilized to further investigate the metabolism of specific WG wheat phytochemicals. The objective of this study was to understand the impact of dietary WG wheat intake on the endogenous metabolome Another aim was to generate new insights into biological mechanisms underlying the health-related effects of WG wheat consumption on major chronic diseases, including cancers, CVD, and diabetes. Efforts were made to identify more specific biomarkers that precisely define dietary exposures and provide better estimates of diet-disease associations

Objectives

Methods

Results

Conclusion