title: Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation.
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.
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. eugene841226@gmail.com.
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Statistics, Seoul National University, Seoul 08826, Korea. huhixoo@gmail.com.
authors.forename: Iksoo
authors.initials: I
authors.lastname: Huh
authors.affiliation: Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Korea. jiyeonk@seoultech.ac.kr.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Sport Science, Korea Institute of Sport Science, Seoul 01794, Korea. saejpark@sports.re.kr.
authors.forename: Saejong
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dankook University, Chungnam 31116, Korea. shryu@glpt.co.kr.
authors.forename: Sung Ha
authors.initials: SH
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Dankook University, Chungnam 31116, Korea. kyubong@dankook.ac.kr.
authors.forename: Kyu-Bong
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea. suhkmann@pusan.ac.kr.
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Statistics, Seoul National University, Seoul 08826, Korea. tspark@stats.snu.ac.kr.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea. orank@ewha.ac.kr.
authors.forename: Oran
authors.initials: O
authors.lastname: Kwon
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D004032:Diet; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis*; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000097:blood; D055432:Metabolomics; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D050177:Overweight / Q000097:blood; D018384:Oxidative Stress; D011379:Prognosis; D012372:ROC Curve; D065856:Rubus / Q000737:chemistry / Q000145:classification; D057185:Sedentary Behavior
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D008315:Malondialdehyde; C022050:phenylacetylglycine; D005978:Glutathione; D005998:Glycine
keywords: inflammation; metabolomics; oxidative stress; prognostic marker; sedentary overweight/obese adults