Milk is a key component in infant nutrition worldwide and, in the Western parts of the world, also in adult nutrition. Milk of bovine origin is both consumed fresh and processed into a variety of dairy products including cheese, fermented milk products, and infant formula. The nutritional quality and processing capabilities of bovine milk is closely associated to milk composition. Metabolomics is ideal in the study of the low-molecular-weight compounds in milk, and this review focuses on the recent nuclear magnetic resonance (NMR)-based metabolomics trends in milk research, including applications linking the milk metabolite profiling with nutritional aspects, and applications which aim to link the milk metabolite profile to various technological qualities of milk. The metabolite profiling studies encompass the identification of novel metabolites, which potentially can be used as biomarkers or as bioactive compounds. Furthermore, metabolomics applications elucidating how the differential regulated genes affects milk composition are also reported. This review will highlight the recent advances in NMR-based metabolomics on milk, as well as give a brief summary of when NMR spectroscopy can be useful for gaining a better understanding of how milk composition is linked to nutritional or quality traits.

Somatic cell count (SCC) is associated with changes in milk composition, including changes in proteins, lipids, and milk metabolites. Somatic cell count is normally used as an indicator of mastitis infection. The compositional changes in protein and fat affect milk coagulation properties, and also the metabolite composition is thought to contribute to differential milk properties. Milk somatic cells comprise different cell types, which may contribute to differential milk metabolite fingerprints. In this study, milk from a relatively large number of individual cows, representing significant differences in SCC, were analyzed by nuclear magnetic resonance (NMR)-based metabonomics, and the milk metabolite profiles were analyzed for differences related to SCC. Global principal component analysis performed on 876 samples from 2 Danish dairy breeds and orthogonal projection of latent structures discriminant analysis performed on a smaller subset (n=70) representing high (SCC >7.2×10(5) cells/mL) and low (SCC <1.4×10(4) cells/mL) milk SCC identified latent variables, which could be attributed to milk with elevated SCC. In addition, partial least squares regression between the NMR milk metabolite profiles and SCC revealed a strong correlation. The orthogonal projection of latent structures discriminant analysis and partial least squares regressions pinpointed specific NMR spectral regions and thereby identification of milk metabolites that differed according to SCC. Relative quantification of the identified metabolites revealed that lactate, butyrate, isoleucine, acetate, and β-hydroxybutyrate were increased, whereas hippurate and fumarate were decreased in milk with high levels of somatic cells.

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by nuclear magnetic resonance (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5–7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery.