Recent progress on health effects and biosynthesis of two key sialylated human milk oligosaccharides, 3'-sialyllactose and 6'-sialyllactose.

Human milk oligosaccharides (HMOs), the third major solid component in breast milk, are recognized as the first prebiotics for health benefits in infants. Sialylated HMOs are an important type of HMOs, accounting for approximately 13% of total HMOs. 3'-Sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) are two simplest sialylated HMOs. Both SLs display promising prebiotic effects, especially in promoting the proliferation of bifidobacteria and shaping the gut microbiota. SLs exhibit several health effects, including antiadhesive antimicrobial ability, antiviral activity, prevention of necrotizing enterocolitis, immunomodulatory activity, regulation of intestinal epithelial cell response, promotion of brain development, and cognition improvement. Both SLs have been approved as "Generally Recognized as Safe" by the American Food and Drug Administration and are commercially added to infant formula. The biosynthesis of SLs using enzymatic or microbial approaches has been widely studied. The enzymatic synthesis of SLs can be realized by two types of enzymes, sialidases with trans-sialidase activity and sialyltransferases. Microbial synthesis can be achieved by the multiple recombinant bacteria in one-pot reaction, which express the enzymes involved in SL synthesis pathways separately or in combination, or by metabolically engineered strains in a fermentation process. In this article, the physiological properties of 3'-SL and 6'-SL are summarized in detail and the biosynthesis of these SLs via enzymatic and microbial synthesis is comprehensively reviewed.