Milk Polysialic Acid Levels Rapidly Decrease in Line with the N-Acetylneuraminic Acid Concentrations during Early Lactation in Dairy Cows

SIMPLE SUMMARY: In addition to their function as energy sources, monosaccharides are used to build complex structured oligo- and polysaccharides, which play numerous essential roles as functional biomolecules. Such bioactive sugars are also key components of milk, since they have positive impacts on intestinal development, the gut microbiome, and an effective immune system, along with the learning and memory ability of offspring. Moreover, milk oligo- and polysaccharides have anti-adhesive properties against pathogenic microorganisms and viruses and are, therefore, important for the health of the mammary gland and the offspring. One key monosaccharide of such oligo- and polysaccharides is the sialic acid N-acetylneuraminic acid (Neu5Ac). Since bovine milk is not only important for calf health but also, in the case of colostrum, as a functional food for humans, it is of particular interest, at which time of lactation the highest amounts of these bioactive molecules are found in bovine milk. Our results demonstrate that on the day of calving, the highest amounts of Neu5Ac and its polymers are present in bovine milk and, thus, the sialic acid-dependent benefits of bovine milk are also highest at this time. ABSTRACT: Sialylated milk oligosaccharides and glycoconjugates have several positive effects on the mucosal barrier, the gut microbiome, and an effective immune system. For this reason, they are important biomolecules for mammary gland health and optimal development of offspring. In milk, the major sialic acid, N-acetylneuraminic acid (Neu5Ac), can be attached as monosialyl-residues or as polymers. To investigate the sialylation processes during lactation of German Holstein cows, we analyzed udder tissue in addition to milk at different time points of lactation. The analysis of the milk samples revealed that both the levels of Neu5Ac and its polymer, polysialic acid (polySia), rapidly decreased during the first three days of lactation, and a high interindividual variance was observed. In mature milk, however, the sialylation status remains relatively constant. The results indicate that mammary gland epithelial cells are one source for milk polySia, since immunohistochemistry of udder tissue exhibited strong polySia staining in these cells. Furthermore, both polysialyltransferases, ST8SiaII and ST8SiaIV, are expressed. Based on known functions of monosialyl residues and polySia, we discuss the potential impact of these biomolecules and the consequences of the heterogeneous sialylation status of milk in relation to udder health and offspring health.