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. 2019 Sep 27;9(10):201.
doi: 10.3390/metabo9100201.

Application of 1H-NMR Metabolomics for the Discovery of Blood Plasma Biomarkers of a Mediterranean Diet

Shirin Macias  1 , Joseph Kirma  2   3 , Ali Yilmaz  4   5 , Sarah E Moore  6 , Michelle C McKinley  7 , Pascal P McKeown  8 , Jayne V Woodside  9   10 , Stewart F Graham  11   12 , Brian D Green  13
Affiliations

Application of 1H-NMR Metabolomics for the Discovery of Blood Plasma Biomarkers of a Mediterranean Diet

Shirin Macias et al. Metabolites. .

Abstract

The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland (MEDDINI) intervention study monitored the adherence of participants to the MD for up to 12 months. This investigation aimed to profile plasma metabolites, correlating each against the MD score of participants (n = 58). Based on an established 14-point scale MD score, subjects were classified into two groups ("low" and "high"). 1H-Nuclear Magnetic Resonance (1H-NMR) metabolomic analysis found that citric acid was the most significant metabolite (p = 5.99 × 10-4*; q = 0.03), differing between 'low' and 'high'. Furthermore, five additional metabolites significantly differed (p < 0.05; q < 0.35) between the two groups. Discriminatory metabolites included: citric acid, pyruvic acid, betaine, mannose, acetic acid and myo-inositol. Additionally, the top five most influential metabolites in multivariate models were also citric acid, pyruvic acid, betaine, mannose and myo-inositol. Metabolites significantly correlated with the consumption of certain food types. For example, citric acid positively correlated fruit, fruit juice and vegetable constituents of the diet, and negatively correlated with sweet foods alone or when combined with carbonated drinks. Citric acid was the best performing biomarker and this was enhanced by paired ratio with pyruvic acid. The present study demonstrates the utility of metabolomic profiling for effectively assessing adherence to MD and the discovery of novel dietary biomarkers.

Keywords: 1H-NMR; Mediterranean diet; biomarkers; dietary patterns; metabolomics.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Multivariate statistical modelling of 1H-Nuclear Magnetic Resonance 1H-NMR metabolomic data. Plots A–C show group separation achieved by principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and partial least squares discriminant analysis (PLS-DA). Red circles (●1) represent patients with high MDS and green circles (●2) represent individuals with low MDS. D: Is the resulting variable importance in project (VIP) plot indicating the 15 most influential metabolites responsible for the observed separation in the PLS-DA model.
Figure 2
Figure 2
Blood levels of citric acid and pyruvic acid and MDS. (A) Citric acid levels positively correlated with MDS, whereas Pyruvic acid levels negatively correlated. (B) A paired metabolite ratio of citric acid and pyruvic acid achieved the greatest area under the receiver operating characteristic (ROC) curve (AUC = 0.74) value which was the best performing biomarker for MDS. Optimal cutoff was represented on the curve with a red dot and with a red horizontal line on the box plot. The box-plot showed that the overall distribution profiles for low MDS (0–4) and high MDS (5–10) were broadly similar but the mean value was 53% higher in the high MDS group. Y-axis represents concentrations (µM). Data were median centred. The mean concentration of each group was indicated with a red diamond.
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