Background Necrotising enterocolitis (NEC) is one of the most common and fatal intestinal disorders in preterm infants. Breast-fed infants are at lower risk for NEC than formula-fed infants, but the protective components in human milk have not been identified. In contrast to formula, human milk contains high amounts of complex glycans. Objective To test the hypothesis that human milk oligosaccharides (HMO) contribute to the protection from NEC. Methods Since human intervention studies are unfeasible due to limited availability of HMO, a neonatal rat NEC model was used. Pups were orally gavaged with formula without and with HMO and exposed to hypoxia episodes. Ileum sections were scored blindly for signs of NEC. Two-dimensional chromatography was used to determine the most effective HMO, and sequential exoglycosidase digestions and linkage analysis was used to determine its structure. Results Compared to formula alone, pooled HMO significantly improved 96-hour survival from 73.1% to 95.0% and reduced pathology scores from 1.98±1.11 to 0.44±0.30 (p<0.001). Within the pooled HMO, a specific isomer of disialyllacto-N-tetraose (DSLNT) was identified to be protective. Galacto-oligosaccharides, currently added to formula to mimic some of the effects of HMO, had no effect. Conclusion HMO reduce NEC in neonatal rats and the effects are highly structure specific. If these results translate to NEC in humans, DSLNT could be used to prevent or treat NEC in formula-fed infants, and its concentration in the mother’s milk could serve as a biomarker to identify breast-fed infants at risk of developing this disorder.

Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.

f Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (n ‫؍‬ 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of Staphylococcus and total HMO content (r ‫؍‬ 0.66). In a follow-up study, we conducted a series of in vitro growth curve experiments utilizing Staphylococcus aureus or Staphylococcus epidermidis and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of Staphylococcus species in the lactating mammary gland. Human milk oligosaccharides (HMO) are complex glycans highly abundant (ϳ5 to 15 g/liter) in human milk (5,6,24). Representing a diverse collection of structures, almost 150 distinct forms of HMO have been identified (42,43). Based upon their structures, HMO can be classified as simple (sialylated or fucosylated lactose compounds made of three sugar units) or complex (composed of differentially sialylated or fucosylated repeats of lacto-N-biose or N-acetyllactosamine linked to a lactose motif). Interestingly, HMO patterns are highly unique to individual women, and their concentrations vary over the course of lactation, with levels peaking in colostrum and lower concentrations in mature milk (8,12,15,39).From an evolutionary standpoint, it is logical that because the mammary gland exerts a substantial amount of energy to produce these compounds, HMO likely promote the fitness of the offspring even though the infant is largely unable to metabolize them (1, 14, 16). Research from several groups suggests the possibility that HMO are capable of interacting with an infant's gastrointestinal microbiota to promote his or her health (10,27,30,35,38). Indeed, some of the first studies in this area noted the capacity of HMO to promote growth of Bifidobacterium bifidum, a species overrepresented in the gastrointestinal tract of the breast-fed, but not formula-fed, infant (17,29,40). Over 50 years later, research has confirmed that the genetic capacity to metabolize these compounds is conserved among bifidobacteria species common in the infant's gastrointestinal tract (38). These findings suggest that HMO may serve a prebiotic function in selectively promoting the...

The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.

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