The Milk Metabolome of Non-secretor and Lewis Negative Mothers

Abstract

Introduction: The functional role of milk for the developing neonate is an area of great interest, and a significant amount of research has been done. However, a lot of work remains to fully understand the complexities of milk, and the variations imposed through genetics. It has previously been shown that both secretor (Se) and Lewis blood type (Le) status impacts the human milk oligosaccharide (HMO) content of human milk. While some studies have compared the non-HMO milk metabolome of Se+ and Se− women, none have reported on the non-HMO milk metabolome of Se− and Le– mothers.Method and Results: To determine the differences in the non-HMO milk metabolome between Se–Le– mothers and other HMO phenotypes (Se+Le+, Se+Le–, and Se–Le+), 10 milk samples from 10 lactating mothers were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Se or Le HMO phenotypes were assigned based on the presence and absence of 6 HMOs generated by the Se and Le genes. After classification, 58 milk metabolites were compared among the HMO phenotypes. Principal component analysis (PCA) identified clear separation between Se–Le– milk and the other milks. Fold change analysis demonstrated that the Se–Le– milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism.Conclusion: The results of this brief research report suggest that the milk metabolome of mothers with the Se–Le– phenotype differs in its non-HMO metabolite composition from mothers with other HMO phenotypes.

Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics

“…Among Americans and Europeans, indeed, 80% of the population express the secretor phenotype [ 33 ], making Group 4 extremely rare. In contrast, in some African populations, over ~38% are non-secretors, with higher probabilities of mothers belonging to Group 4 [ 39 ].…”

“…Different authors were able to differentiate breast milk on the basis of the secretor and non-secretor phenotype, regardless of the different metabolomics technology applied. Their studies demonstrated the abundance of α1-2 fucosylated HMOs (2′-FL, LNFP-I) in secretor’s milk and the absence of α1-2 fucosylated HMOs in non-secretor’s milk [ 39 , 40 , 123 , 126 , 127 , 133 ].…”

“…Moreover, Sammuel et al also correlated higher concentrations of LNT and LNnT in the milk of overweight mothers compared to those observed in milk from mothers with normal pre-pregnancy BMI (ppBMI) [ 39 ]. This aspect was also recently investigated by Saben et al [ 135 ], who demonstrated that HMO composition differs among mothers with normal weight, overweight or obesity.…”

“…Recently, Wang et al [ 39 ] have performed a study on a cohort of 10 healthy breast-feeding mothers. First, they have confirmed previously reported results in terms of HMO composition related to different genotypes.…”

“…In conclusion, metabolomics was useful to investigate the protective role of HMOs against HIV transmission [ 6 ], to characterize specific patterns of HMOs related to genotypes [ 39 , 40 , 123 , 126 , 127 , 133 ] and to support the hypothesis that HMO content in breastmilk varies according to the gestational age and the stage of lactation [ 14 , 114 , 129 , 130 ], and that there are differences in HMO production and secretion according to the location and the ethnicity of the women [ 132 , 134 ].…”