Discovery Of Novel Biomarkers Of Whole Grain Rye In A Dietary Intervention Study Through Metabolomics

Pekka KESKI-RAHKONEN, IARC, France
HANHINEVA K. 2 , KOLEHMAINEN M. 2 , MYKKÄNEN H. 2 , POUTANEN K. 3 , SCALBERT A. 1

1 Biomarkers Group, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France
2 Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
3 VTT Technical Research Centre of Finland, Espoo, Finland

Purpose: Intake of dietary fiber, in particular cereal fiber, is associated with a reduced risk of colorectal cancer. However, the role of subtypes of cereals is unclear and accurate measurement of the intake of specific whole grains is difficult with traditional dietary assessment methods. Our aim was to employ untargeted metabolomics to find molecular biomarkers of intake for whole grain rye, a significant source of dietary fiber in the Nordic countries.
 
Methods: Fifteen free-living subjects completed an intervention with a 4-week run-in and two 4-week test periods in cross-over design. White wheat bread (WW, 3% fiber) was consumed during the run-in, followed by whole grain rye bread (WGR) and white wheat bread enriched with bioprocessed rye bran (WW+BRB) (both 10% fiber). Fasting plasma samples were collected after each period and analyzed by high resolution mass spectrometry coupled with an UHPLC system. Data preprocessing was performed using Agilent feature finding workflow and the discriminant features were found using univariate differential analysis.
 
Results: After WGR period, 22 compounds showed significantly increased plasma concentration when compared to WW period (q ≤ 0.1, fold change ≥ 1.5). After WW+BRB period, mean concentrations of all the 22 compounds were significantly higher or comparable to the WGR period. Eleven compounds could be identified, including 2-aminophenolsulphate and several conjugated alkylresorcinols such as 5-nonadecyl-1,3-benzenediol. For three alkylresorcinols, both sulphate and glucuronide conjugates were observed.
 
Conclusions: We found 2-aminophenol sulphate and metabolites of alkylresorcinols as potential biomarkers for wholegrain rye intake. Bioprocessed rye bran yielded similar results confirming bran as the main source for these compounds. Validation of these markers in population studies is needed together with similar studies to find biomarkers for other sources of cereal fiber.
  
Funding source: IARC Postdoctoral Fellowship, EU-FP7 Cofund, Eurocan.