Recent Advances on Lacto-N-neotetraose, a Commercially Added Human Milk Oligosaccharide in Infant Formula

Human milk oligosaccharides (HMOs) act as the important prebiotics and display many unique health effects for infants. Lacto-N-neotetraose (LNnT), an abundant HMO, attracts increasing attention because of its unique beneficial effects to infants and great commercial importance. It occurs in all groups of human milk, but the concentration generally decreases gradually with the lactation period. It has superior prebiotic property for infants, and its other health effects have also been verified, including being immunomodulatory, anti-inflammatory, preventing necrotizing enterocolitis, antiadhesive antimicrobials, antiviral activity, and promoting maturation of intestinal epithelial cells. Safety evaluation and clinical trial studies suggest that LNnT is safe and well-tolerant for infants. It has been commercially added as a functional ingredient in infant formula. LNnT can be synthesized via chemical, enzymatic, or cell factory approachs, among which the metabolic engineering-based cell factory synthesis is considered to be the most practical and effective. In this article, the occurrence and physiological effects of LNnT were reviewed in detail, the safety evaluation and regulation status of LNnT were described, various approaches to LNnT synthesis were comprehensively summarized and compared, and the future perspectives of LNnT-related studies were provided.