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Nutrients 2017, 9(3), 233; doi:10.3390/nu9030233

Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation

1
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea
2
Department of Statistics, Seoul National University, Seoul 08826, Korea
3
Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Korea
4
Department of Sport Science, Korea Institute of Sport Science, Seoul 01794, Korea
5
College of Pharmacy, Dankook University, Chungnam 31116, Korea
6
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea
*
Authors to whom correspondence should be addressed.
Received: 16 January 2017 / Revised: 19 February 2017 / Accepted: 28 February 2017 / Published: 4 March 2017
(This article belongs to the Special Issue Precision Nutrition and Metabolic Syndrome Management)
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Abstract

Various statistical approaches can be applied to integrate traditional and omics biomarkers, allowing the discovery of prognostic markers to classify subjects into poor and good prognosis groups in terms of responses to nutritional interventions. Here, we performed a prototype study to identify metabolites that predict responses to an intervention against oxidative stress and inflammation, using a data set from a randomized controlled trial evaluating Korean black raspberry (KBR) in sedentary overweight/obese subjects. First, a linear mixed-effects model analysis with multiple testing correction showed that four-week consumption of KBR significantly changed oxidized glutathione (GSSG, q = 0.027) level, the ratio of reduced glutathione (GSH) to GSSG (q = 0.039) in erythrocytes, malondialdehyde (MDA, q = 0.006) and interleukin-6 (q = 0.006) levels in plasma, and seventeen NMR metabolites in urine compared with those in the placebo group. A subsequent generalized linear mixed model analysis showed linear correlations between baseline urinary glycine and N-phenylacetylglycine (PAG) and changes in the GSH:GSSG ratio (p = 0.008 and 0.004) as well as between baseline urinary adenine and changes in MDA (p = 0.018). Then, receiver operating characteristic analysis revealed that a two-metabolite set (glycine and PAG) had the strongest prognostic relevance for future interventions against oxidative stress (the area under the curve (AUC) = 0.778). Leave-one-out cross-validation confirmed the accuracy of prediction (AUC = 0.683). The current findings suggest that a higher level of this two-metabolite set at baseline is useful for predicting responders to dietary interventions in subjects with oxidative stress and inflammation, contributing to the emergence of personalized nutrition. View Full-Text
Keywords: oxidative stress; inflammation; prognostic marker; metabolomics; sedentary overweight/obese adults oxidative stress; inflammation; prognostic marker; metabolomics; sedentary overweight/obese adults
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kim, Y.J.; Huh, I.; Kim, J.Y.; Park, S.; Ryu, S.H.; Kim, K.-B.; Kim, S.; Park, T.; Kwon, O. Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation. Nutrients 2017, 9, 233.

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