ABSTRACT

Human milk oligosaccharides (HMOs) are a class of biologically active components abundant in breast milk, which have drawn significant attention because of their essential role in the healthy development of infants. Among the identified HMOs, lacto-N-neotetraose (LNnT) is one of the most important and abundant neutral core HMOs, and LNnT exhibits diverse health benefits, including prebiotic, immune-modulatory, anti-inflammatory, preventive necrotizing small intestinal colitis, and intestinal epithelial maturation-promoting effects. LNnT has received safety approvals from several food safety regulators and has been approved to be added as a functional ingredient to infant formulas, showing great commercial value and prompting a growing interest in the state of research on LNnT. Based on this, we systematically reviewed the recent progress of LNnT research under four aspects: the physiological functions of LNnT, the synthesis methods of LNnT (chemical, enzymatic and microbial synthesis), the important rate-limiting enzymes required for LNnT synthesis, and the future prospects of LNnT synthesis.