Human milk oligosaccharides: a novel method provides insight into human genetics

Area of Science:

• Human milk oligosaccharide analysis
• Human genetics
• Glycobiology

Background:

• Human milk is a rich source of oligosaccharides, with their composition influenced by donor genetics.
• Lewis blood group and secretor antigen status are key genetic determinants of human milk oligosaccharide profiles.

Purpose of the Study:

• To develop and validate a method for quantifying neutral human milk oligosaccharides.
• To investigate the relationship between human milk oligosaccharide profiles and donor genetics (Lewis blood group and secretor status).

Main Methods:

• A novel method involving centrifugation-filtration, lactose removal, and high-pH anion-exchange chromatography was employed.
• Quantitative analysis of oligosaccharides, including lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNneoT), was performed on 386 milk samples.
• Carbohydrate-binding probes were used to study milk glycoproteins.

Main Results:

• The developed method accurately quantifies neutral human milk oligosaccharides and provides genetic footprints of donor Lewis and secretor status.
• Oligosaccharide profiles were confirmed as accurate predictors of Lewis blood group status.
• Unusual oligosaccharide profiles, not predicted by known genotypes, were observed, highlighting complex genetic interactions.

Conclusions:

• Human milk oligosaccharide analysis offers a non-invasive method to determine donor Lewis blood group and secretor status.
• The study confirms the tissue specificity of Lewis-related antigens and the exquisite specificity of glycosyltransferases.
• Findings have implications for understanding infant health and epidemiological studies involving breast-fed infants.