How far is it from infant formula to human milk? A look at the human milk oligosaccharides

Human milk oligosaccharides (HMOs), a group of structurally diverse unconjugated glycans in breast milk, act as important prebiotics and have plenty of unique health effects for growing infants. 2′-Fucosyllactose (2′-FL) is the most abundant HMO, accounting for approximately 30%, among approximately 200 identified HMOs with different structures. 2′-FL can be enzymatically produced by α1,2-fucosyltransferase, using GDP-l-fucose as donor and lactose as acceptor. Metabolic engineering strategies have been widely used for enhancement of GDP-l-fucose supply and microbial production of 2′-FL with high productivity. GDP-l-fucose supply can be enhanced by two main pathways, including de novo and salvage pathways. 2′-FL-producing α1,2-fucosyltransferases have widely been identified from various microorganisms. Metabolic pathways for 2′-FL synthesis can be basically constructed by enhancing GDP-l-fucose supply and introducing α1,2-fucosyltransferase. Various strategies have been attempted to enhance 2′-FL production, such as acceptor enhancement, donor enhancement, and improvement of the functional expression of α1,2-fucosyltransferase. In this review, current progress in GDP-l-fucose synthesis and bacterial α1,2-fucosyltransferases is described in detail, various metabolic engineering strategies for enhancing 2′-FL production are comprehensively reviewed, and future research focuses in biotechnological production of 2′-FL are suggested.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Strategies for Enhancing Microbial Production of 2′-Fucosyllactose, the Most Abundant Human Milk Oligosaccharide

Liu

Zhu

Wang³

et al. 2022

“…14 The different structures determine the function of HMOs, and their relative abundances may determine the overall effect of a complex HMO mixture. 15 Therefore, quantitative analysis of HMOs can reveal their role during development.…”

Section: ■ Introductionmentioning

confidence: 99%

Pregnancy-Related Diseases and Delivery Mode can Affect the Content of Human Milk Oligosaccharides: A Preliminary Study

Wang

Liu

et al. 2022

Human milk oligosaccharides (HMOs) are the second most abundant carbohydrates in colostrum. In this study, we performed a quantitative analysis of 13 oligosaccharides in 99 colostrum samples obtained from mothers living in Northwest China. The analysis combined liquid chromatography-mass spectrometry (LC-MS) with 2-amino-N-(2-aminoethyl)benzamide (AEAB) labeling and nonsecretors accounted for 17%. Compared with healthy secretor mothers, those with gestational diabetes mellitus presented lower levels of sialylated oligosaccharides, especially 3′-sialyllactose. Colostrum from mothers with pregnancy-induced hypertension had higher levels of fucosylated oligosaccharides, but the difference was not significant, and hypothyroidism appeared to have no effect on HMOs. Most HMOs (especially 6′-sialyllactose) were more abundant in colostrum from mothers who underwent vaginal delivery than a C-section. These findings show that the concentration of total or individual HMOs is affected by multiple factors. These findings provide a reference for evaluating variations in HMO expression among different populations and potential guidance for providing personalized clinical nutrition.

“…HMOs can not only indirectly influence the immune system of infants by shaping the intestinal microbiota but also directly regulate the immune responses by affecting different cell populations or modulating inflammatory gene expression. 1 The cell-free supernatant from B. infantis fermentation broth using LNnT was evaluated for anti-inflammatory activity on Caco-2 cells. 67 It is suggested that LNnT possesses immunomodulatory ability and induces the formation of the anti-inflammatory mediators to restrain the inflammatory responses.…”

Section: Physiological Propertiesmentioning

confidence: 99%

“…Breast-fed infants show significant advantages in long-term health and intelligence over formula-fed infants. 1 However, when breastfeeding is medically contraindicated, mothers give up breastfeeding, or mothers do not have enough breast milk, the infant formula becomes the infant food in whole or in part. In 1867, the first commercial infant formula appeared in the world.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Zhu

et al. 2022

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 welltolerant 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.