## 2 The NMR-Based Metabolomics in Food Science and the Foodomics Approach  
It is important, before exploring the potentiality of the NMR in metabolomics studies, to clarify what metabolomics studies are. The term \"metabolomics\" was introduced by [PERSON] and defined as a comprehensive and quantitative analysis of all metabolites in a system [22]. On the other hand, the term \"metabolomics\" was coined by [PERSON] in 1999 [23], and it represents \"the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification.\" Nowadays, modern metabolic phenotyping (metabotyping) is known as metabolomics, \begin{table}
\begin{tabular}{c c c} \hline \hline  & **NMR** & **MS** & **Is NMR ‘Greener’** \\  & Low sensitivity (can & High sensitivity \\  & be improved using & (nanomolar); \\  & microfluidics, & Can be used for both \\  & dynamic nuclear & selective (targeted) \\  & polarization,... ); & and nonselective \\  & Generally used for & (nontargeted) \\  & nonselective analysis & analyses \\ \hline  & All metabolites that & Usually needs \\  & have NMR & different \\  & concentration level & chromatography \\  & can be detected in one & techniques for \\  & measurement & different classes of \\  & & metabolites \\ \hline  & & \(\geq\)300 (depending on \\  & detectable & MS techniques, \\  & spectral resolution & whether GC-MS or \\  & LC-MS is used) \\ \hline  & & \\
**Reproducibility** & Very high & Moderate \\ \hline  & & \(\quad\)Complex (needs \\  & & different columns and \\  & & ionization methods) \\ \hline  & Not required (tissues \\  & can be analyzed & Yes, requires tissue \\  & directly using & extraction \\  & HRMAS NMR) & \\ \hline  & & Nondestructive; \\  & sample can be & \\  & recovered and stored & Destructive technique \\  & for a long time; & but need a small \\  & several analyses can & amount of sample \\  & be carried out on the & \\  & same sample & \\ \hline  & & Longer (requires \\  & Fast (the entire & different \\  & sample can be & chromatography \\  & analyzed in one & techniques depending \\  & measurement) & on the metabolites \\  & & analyzed) \\ \hline  & & High cost per sample, \\  & & more expensive than \\  & & NMR \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Key differences between NMR and MS as green tools for metabolomics research (adapted from [PERSON] [17]). encompassing both the comprehensive analysis of the small molecule content of the tested samples, and the changes that occur in response to a stimulus of one sort or another (physiological, pharmacological, or toxicological) [24]. The given definition points out the importance of the HR-NMR in \"the augmentation and complementation of the information provided by measuring the genetic and proteomic responses to xenobotic exposure\" as it is appropriate \"for investigating abnormal body fluid compositions\", as a wide range of metabolites can be quantified simultaneously with no sample preparation and \"without prejudice\" [23]. In this light, [PERSON] describes de facto the NMR-based metabolomics approach. In summary, it represents a high-performance fingerprinting process that examines the entire collection of small molecules (typically \(<\)1800 Dalton) that are present in a concentration above 10 \(\upmu\)M, including sugars, amino acids, organic acids, and lipids, and is called'metabolome' [25]. In summary, metabolomics is the final step of a more structured pipeline that involves more omics platforms, such as proteomics, transcriptomics, and genomics [22], as represented in Figure 2.  
This integrated \"snapshot\" may change throughout the exposure to external factors or during organism development. When dealing with this technique, almost two kinds of approaches can be used for the analysis of the metabolome: (i) the target analysis, which is metabolic profiling, and (ii) pattern analysis, which is metabolic and metabonomic fingerprinting.