Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated glycans that are highly abundant in and unique to human milk. Originally, HMOs were discovered as a prebiotic "bifidus factor" that serves as a metabolic substrate for desired bacteria and shapes an intestinal microbiota composition with health benefits for the breast-fed neonate. Today, HMOs are known to be more than just "food for bugs". An accumulating body of evidence suggests that HMOs are antiadhesive antimicrobials that serve as soluble decoy receptors, prevent pathogen attachment to infant mucosal surfaces and lower the risk for viral, bacterial and protozoan parasite infections. In addition, HMOs may modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, lower the risk for necrotizing enterocolitis and provide the infant with sialic acid as a potentially essential nutrient for brain development and cognition. Most data, however, stem from in vitro, ex vivo or animal studies and occasionally from association studies in mother-infant cohorts. Powered, randomized and controlled intervention studies will be needed to confirm relevance for human neonates. The first part of this review introduces the pioneers in HMO research, outlines HMO structural diversity and describes what is known about HMO biosynthesis in the mother's mammary gland and their metabolism in the breast-fed infant. The second part highlights the postulated beneficial effects of HMO for the breast-fed neonate, compares HMOs with oligosaccharides in the milk of other mammals and in infant formula and summarizes the current roadblocks and future opportunities for HMO research.

Human milk oligosaccharides: Every baby needs a sugar mama

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

/pdf/enteral-nutrient-supply-for-preterm-infants-commentary-from-3s5hnnsw5i.pdf

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition

In this Review, Martens and colleagues describe how dietary and endogenous glycans shape the composition of the gut microbiota and how individual microorganisms degrade these glycans. They also highlight the potential to influence this ecosystem for better health and nutrition.

How glycan metabolism shapes the human gut microbiota

Human breast milk: A review on its composition and bioactivity.

http://ssu.ac.ir/cms/fileadmin/user_upload/Mtahghighat/tfood/ARTICLES/milk/The_human_milk_microbiota_Origin_and_potential_roles_in_health_and_disease.pdf

The human milk microbiota: origin and potential roles in health and disease.

This study aimed to examine the carbohydrate content (monosaccharides, lactose, and oligosaccharides) of human milk over 4 months of lactation to determine whether any changes occurred over time. Milk samples from 46 mothers, who delivered at term, were collected at 4th, 10th, 30th, 60th, 90th, and 120th days after delivery. Carbohydrates were measured by high-pressure liquid chromatography. Mean lactose concentration (+/- SD) increased from 56 +/- 6.06 g/L on day 4 to 68.9 +/- 8.16 g/L on day 120. Oligosaccharide level decreased from 20.9 +/- 4.81 g/L to 12.9 +/- 3.30 g/L, respectively. Monosaccharides represented only 1.2% of total carbohydrates. The changes in carbohydrate composition found indicate that carbohydrate synthesis by the mammary gland is a dynamic process. The physiological and biological relevance of human milk oligosaccharides is also discussed.

Changes in carbohydrate composition in human milk over 4 months of lactation

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l(-1)) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.

Oligosaccharides in human milk during different phases of lactation.

Summary: The aim of the study was to investigate the effect of age and feeding pattern on intestinal permeability during the first month of life. The subjects were 72 full-term, healthy neonates who were (a) exclusively breast-fed (BF group, n = 36) or (b) artificially fed (CM group, n = 36) with ei

Intestinal Permeability. Changes during the First Month: Effect of Natural versus Artificial Feeding

Objectives The aim of this study was to identify a link between the total amount of breast milk oligosaccharides and faecal microbiota composition of newborns at the end of the first month of life, with special attention paid to bifidobacteria, and establish the role, if any, of the different oligosaccharides in determining the gut microbiota composition. Subjects and methods Milk oligosaccharide groups were identified by high-performance anion exchange chromatography analysis. DPCRNA from newborns' faecal samples at 30 days of life was isolated and processed by polymerase chain reaction analyses that allow the identification of 6 species of bifidobacteria (adolescentis, bifidum, breve, catenulatum, longum, infantis) and Ruminococcus spp; denaturing gradient gel electrophoresis analysis was also performed. Results No substantial differences in bifidobacteria species composition within milk groups 1, 2, and 3 were observed; however, infants fed with group 4 milk show a microbiota characterised by a greater frequency of Bifidobacteria adolescentis and the absence of Bifidobacteria catenulatum. For the first time, a high percentage of the Ruminococcus genus in infants fed with all milk groups was found. Conclusions Our data show that milk groups 1, 2, and 3, containing an amount of oligosaccharides ranging within 10 to 15 g/L, share a substantially identical composition of the intestinal microbiota in breast-fed infants, despite quali-quantitative difference in oligosaccharides content. Newborns taking milk with only 5 g/L of oligosaccharides (group 4) harbour a different intestinal microbiota.

Oligosaccharides in 4 different milk groups, Bifidobacteria, and Ruminococcus obeum.

We report on a male with intestinal lymphangiectasia, mild mental retardation, seizures, and a typical face; the syndrome was first delineated by Hennekam et al., Am. J. Med. Genet. 34:593-600 [1989]. His parents are consanguineous. This case seems to confirm the existence of the Hennekam syndrome.

Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome.

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