Synthetic Disialyl Hexasaccharides Protect Neonatal Rats from Necrotizing Enterocolitis

Yu, Hai; Lau, Kam; Thon, Vireak; Autran, Chloe; Jantscher-Krenn, Evelyn; Xue, Mengyang; Li, Yanhong; Sugiarto, Go; Qu, Jingyao; Mu, Shengmao; Ding, Li; Bode, Lars; Chen, Xi

doi:10.1002/anie.201403588

Cited by 73 publications

(98 citation statements)

References 35 publications

(50 reference statements)

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“…Over the past two decades, we have learned that these molecules are of great importance to infant health and development. [34, 44, 120, 194] While major advances have been made in producing authentic samples of HMOs, these compounds are currently not used as additives to infant food products. Their production, using both chemical and chemoenzymatic strategies is a frontier topic in synthetic carbohydrate chemistry.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…[195, 196] In addition to being easier to synthesize than native HMOs, these unnatural glycoconjugates have been shown to reduce necrotizing enterocolitis in neonatal rats. [44] Ultimately, the field of carbohydrate prebiotics will continue to pursue products that assist in allowing the formula-fed infant to develop a microbiome mirroring the breast fed infant.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Infant food applications of complex carbohydrates: Structure, synthesis, and function

Ackerman

Craft

Townsend

2017

Carbohydrate Research

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Professional health bodies such as the World Health Organization (WHO), the American Academy of Pediatrics (AAP), and the U.S. Department of Health and Human Services (HHS) recommend breast milk as the sole source of food during the first year of life. This position recognizes human milk as being uniquely suited for infant nutrition. Nonetheless, most neonates in the West are fed alternatives by 6 months of age. Although inferior to human milk in most aspects, infant formulas are able to promote effective growth and development. However, while breast-fed infants feature a microbiota dominated by bifidobacteria, the bacterial flora of formula-fed infants is usually heterogeneous with comparatively lower levels of bifidobacteria. Thus, the objective of any infant food manufacturer is to prepare a product that results in a formula-fed infant developing a breast-fed infant-like microbiota. The goal of this focused review is to discuss the structure, synthesis, and function of carbohydrate additives that play a role in governing the composition of the infant microbiome and have other health benefits.

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Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Infant food applications of complex carbohydrates: Structure, synthesis, and function

Ackerman

Craft

Townsend

2017

Carbohydrate Research

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“…Therefore, it is critical to identify medical and nutritional strategies to protect formulafed preterm infants against NEC development. Modulations of the gut microbiota with pre-and probiotics may decrease NEC risk, but important questions related to type and dose of different products and their optimal time of administration remain unclear (10,18,23,46).…”

mentioning

confidence: 99%

Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs

Birck

Nguyen

Cilieborg

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Birck MM, Nguyen DN, Cilieborg MS, Kamal SS, Nielsen DS, Damborg P, Olsen JE, Lauridsen C, Sangild PT, Thymann T. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. Am J Physiol Gastrointest Liver Physiol 310: G323-G333, 2016. First published December 17, 2015 doi:10.1152/ajpgi.00392.2015.-Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90 -92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n ϭ 16 -17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59 -63%) in CON and PAR pigs (P Ͻ 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P Ͻ 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P Ͻ 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formulafed preterm neonates.

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“…4 These protective measures are due, in part, to the human milk oligosaccharides (HMOs), a family of unconjugated glycans unique to human milk. 8–13 …”

Section: Introductionmentioning

confidence: 99%

“…Although the general functionings of pooled HMOs have been explored, the functional roles of individual HMOs are far less clear due to a limited access to large quantities of single-entity HMOs. 8,11 …”

Section: Introductionmentioning

confidence: 99%

Synthesis of lacto- N -tetraose

Craft

Townsend

2017

Carbohydrate Research

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Human milk oligosaccharides (HMOs) are the third largest macromolecular component of breast milk and offer infants numerous health benefits, most of which stem from the development of a healthy microbiome. Characterization, quantification, and chemical derivatization of HMOs remains a frontier issue in glycobiology due to the challenge of isolating appreciable quantities of homogenous HMOs from breast milk. Herein, we report the synthesis of the human milk tetrasaccharide lacto-N-tetraose (LNT). LNT is ubiquitous in human breast milk as it is a core structure common to longer-chain HMOs and many glycolipids.

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Synthetic Disialyl Hexasaccharides Protect Neonatal Rats from Necrotizing Enterocolitis

Cited by 73 publications

References 35 publications

Infant food applications of complex carbohydrates: Structure, synthesis, and function

Infant food applications of complex carbohydrates: Structure, synthesis, and function

Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs

Synthesis of lacto- N -tetraose

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