The Human Milk Metabolome Reveals Diverse Oligosaccharide Profiles

Abstract

Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (<20%), including lactose, urea, glutamate, myo-inositol, and creatinine. Principal components analysis identified 2 clear groups of participants who were differentiable on the basis of milk oligosaccharide concentration and who were classified as secretors or nonsecretors of fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'-fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of the interrelations between the milk sugars by using Spearman rank correlations revealed significant positive and negative associations, including positive correlations between fucose and products of the FUT2 gene and negative correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene. The total concentration of milk oligosaccharides was conserved among participants (%CV = 18%), suggesting tight regulation of total oligosaccharide production; however, concentrations of specific oligosaccharides varied widely between participants (%CV = 30.4-84.3%). The variability in certain milk metabolites suggests possible roles in infant or infant gut microbial development. This trial was registered at clinicaltrials.gov as NCT01817127.

Lactation and Intestinal Microbiota: How Early Diet Shapes the Infant Gut

“…Infants that are breast fed by secretor mothers are protected from moderate-to-severe diarrhea caused by a variety of enteric pathogens, ostensibly the HMOs act as decoy binding sites for the pathogens thus reducing access to epithelial binding sites [72,75]. This is possible because secretor mothers produce more free milk oligosaccharides in terms of both structural diversity and total amount produced compared to non-secretor mothers [72,73]. However, there is a great deal of functional redundancy in lactation.…”

“…Lewis blood type and secretor status determine the structure and concentration of fucosylated oligosaccharides providing a clear example of how maternal genotype can affect milk composition and, subsequently, the infant gut microbiota [72,73]. Women who possess a functional FUT2 gene, i.e., who express detectable levels of α-1,2-fucosyltransferase, in body fluids such as tears, saliva, and milk are called secretors.…”

Safety of 2′‐O‐fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97

“…The applicant provided several publications on the 2'-FL content in human milk in relation to secretorand Lewis-blood group status (Thurl et al, 1997;Galeotti et al, 2012Galeotti et al, , 2014, ethnicity (Erney et al, 2000;Musumeci et al, 2006), lactation period (Coppa et al, 1999;Erney et al, 2000;Sumiyoshi et al, 2003;Asakuma et al, 2008;Leo et al, 2010;Bao et al, 2013), preterm birth (Nakhla et al, 1999;Gabrielli et al, 2011), and in mature milk (Chaturvedi et al, 1997(Chaturvedi et al, , 2001aErney et al, 2000Erney et al, , 2001Sumiyoshi et al, 2003;Morrow et al, 2004;Leo et al, 2010;Thurl et al, 2010;Asakuma et al, 2011;Coppa et al, 2011;Galeotti et al, 2012;Smilowitz et al, 2013;Hong et al, 2014). The concentration of 2'-FL in breast milk appears to depend on the lactation period, with higher levels reported in colostrum and decreased levels observed thereafter (Erney et al, 2000).…”

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis

“…It is interesting to note that, although HMOs are intrinsic to mother's milk, the composition is not universal. One study that investigated the constituents of milk samples from 52 mothers at 34-38 wk of gestation showed that, although there were a number of conserved metabolites between subjects, there was great variability in the types of oligosaccharides present (44).…”

“…There are many sugars present in human milk, the most abundant components being lactose and oligosaccharides (44). The gut microbial composition is influenced by humanmilk oligosaccharides (HMOs), which are an abundant and diverse family of glycans.…”