Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

Rudloff, Silvia; Pohlentz, Gottfried; Diekmann, L; Egge, Heinz; Kunz, Clemens

doi:10.1111/j.1651-2227.1996.tb14095.x

Cited by 131 publications

(83 citation statements)

References 27 publications

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“…If we assume that also under these conditions neutral and acidic HMOs pass the epithelium via paracellular pathways, this process could explain why Rudloff et al (7) as well as Obermeier et al (8) were able to detect both neutral and acidic oligosaccharides in the urine of human milk-fed infants. How the additional transcytosis of neutral HMOs affects their absorption and whether this process might be related to the presentation of these components to lymphatic cells present in the vicinity of the epithelial cells remain to be established.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, we have shown that these oligosaccharides are only minimally digested by enzymes of the upper gastrointestinal tract (6). Furthermore, neutral as well as acidic HMOs could be detected in the urine of breast-fed but not in that of formulafed infants (7,8) suggesting that they are absorbed in the intestine. These findings raise the question of how and to what extent these components pass the epithelium of the small intestine.…”

mentioning

confidence: 99%

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Investigations of the in Vitro Transport of Human Milk Oligosaccharides by a Caco-2 Monolayer Using a Novel High Performance Liquid Chromatography-Mass Spectrometry Technique

Gnoth

Rudloff²,

Kunz³

et al. 2001

Journal of Biological Chemistry

101

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Complex lactose-derived oligosaccharides belong to the main components of human milk and are believed to exert multiple functions in the breast-fed infant. Therefore, we investigated the transepithelial transport of human milk oligosaccharides over Caco-2 monolayers. Main human milk oligosaccharides (HMOs) in the apical, basolateral, or intracellular compartment were separated by high performance liquid chromatography using a Hypercarb TM column and analyzed on line by mass spectrometry. This method allowed the identification and quantification of these components in intra-and extracellular fractions without prior purification. Using this technique we were able to show that acidic and neutral HMOs cross the epithelial barrier. The transepithelial flux of neutral, but not acidic, oligosaccharides was temperature-sensitive and partly inhibited by brefeldin A and bafilomycin A. Furthermore, net flux from the apical to the basolateral compartment was only observed for the neutral components. Similarly, apical cellular uptake was only found for neutral components but not for acidic oligosaccharides. Intracellular concentrations of neutral HMOs were significantly increased by inhibitors of transcytosis such as brefeldin A, N-ethylmaleimide, or bafilomycin A. The cellular uptake was saturable, and an apparent K m for lacto-N-fucopentaose I of 1.7 ؎ 0.1 mmol/liter and for lacto-N-tetraose of 1.8 ؎ 0.4 mmol/liter was determined. Furthermore, the uptake of lacto-N-fucopentaose I could be inhibited by the addition of the stereoisomer lacto-N-fucopentaose II but not by lacto-N-tetraose. These findings suggest that neutral HMOs are transported across the intestinal epithelium by receptor-mediated transcytosis as well as via paracellular pathways, whereas translocation of acidic HMOs solely represents paracellular flux.Oligosaccharides are the third most abundant soluble fraction within human milk. With exception of the elephant, no other mammalian milk contains as many lactose-derived complex oligosaccharides (1). Thus far, more than 100 lactose-derived oligosaccharides have been characterized within human milk (2). HMOs 1 are postulated to be involved in immunomodulation (3, 4) by acting as soluble receptor analogues for bacterial and viral adhesion molecules in the gastrointestinal and the urogenital tract (5) and to stimulate a bifidus flora within the colon. At present little is known about the metabolism of HMOs in the breast-fed neonate. Recently, we have shown that these oligosaccharides are only minimally digested by enzymes of the upper gastrointestinal tract (6). Furthermore, neutral as well as acidic HMOs could be detected in the urine of breast-fed but not in that of formulafed infants (7,8) suggesting that they are absorbed in the intestine. These findings raise the question of how and to what extent these components pass the epithelium of the small intestine. Therefore, we performed in vitro transport studies using the human cell line Caco-2 that displays biochemical and morphological characteristics of differe...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Investigations of the in Vitro Transport of Human Milk Oligosaccharides by a Caco-2 Monolayer Using a Novel High Performance Liquid Chromatography-Mass Spectrometry Technique

Gnoth

Rudloff²,

Kunz³

et al. 2001

Journal of Biological Chemistry

101

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“…There are more than ninety different oligosaccharides, which are produced in the mammary glands. Only about 1 % is absorbed and appears in the urine (Rudloff et al 1996). These oligosaccharides seem to affect the composition of the gut microflora and may partly explain why breast-fed children carry potentially pathogenic E. coli, Klebsiella and other Enterobacteriacae strains less often than nonbreast-fed children (Gothefors et al 1975;Uauy & Araya, 2004).…”

Section: Lactoferrinmentioning

confidence: 99%

Session 1: Feeding and infant development Breast-feeding and immune function

2007

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The newborn receives, via the placenta, maternal IgG antibodies against the microbes present in its surroundings, but such antibodies have a pro-inflammatory action, initiating the complement system and phagocytes. Although the host defence mechanisms of the neonate that involve inflammatory reactivity are somewhat inefficient, this defence system can still have catabolic effects. Breast-feeding compensates for this relative inefficiency of host defence in the neonate by providing considerable amounts of secretory IgA antibodies directed particularly against the microbial flora of the mother and her environment. These antibodies bind the microbes that are appearing on the infant's mucosal membranes, preventing activation of the pro-inflammatory defence. The major milk protein lactoferrin can destroy microbes and reduce inflammatory responses. The non-absorbed milk oligosaccharides block attachment of microbes to the infant's mucosae, preventing infections. The milk may contain anti-secretory factor, which is anti-inflammatory, preventing mastitis in mothers and diarrhoea in infants. Numerous additional factors in the milk are of unknown function, although IL-7 is linked to the larger size of the thymus and the enhanced development of intestinal Tgd lymphocytes in breast-fed compared with non-breast-fed infants. Several additional components in the milk may help to explain why breast-feeding can reduce infant mortality, protecting against neonatal septicaemia and meningitis. It is therefore important to start breast-feeding immediately. Protection is also apparent against diarrhoea, respiratory infections and otitis media. There may be protection against urinary tract infections and necrotizing enterocolitis, and possibly also against allergy and certain other immunological diseases, and tumours. In conclusion, breast-feeding provides a very broad multifactorial anti-inflammatory defence for the infant.

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“…To evaluate the optimal antigen concentrations within a range mimicking physiologic conditions (3,11,23,24) and to exclude possible cytotoxic effects of the investigated substances on CBMC, proliferation assays were performed as previously described (21,22,25). Because neither cytotoxic effects nor a significant proliferative response were detected, nHMOs and LMWF were applied at a concentration of 10 g/mL and aHMOs at 1 g/mL.…”

Section: Oligosaccharides and Cytokine Productionmentioning

confidence: 99%

Human Milk–Derived Oligosaccharides and Plant-Derived Oligosaccharides Stimulate Cytokine Production of Cord Blood T-Cells In Vitro

et al. 2004

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Human milk contains large amounts of free oligosaccharides (HMOs). HMOs have been shown to exert antiinflammatory properties, and evidence for their immunomodulatory effects is increasing. The purpose of this study was to evaluate influences of two human breast milk-derived oligosaccharide samples (neutral and acidic oligosaccharides), and of a low-molecularweight fucoidan on cytokine production and activation of cord blood mononuclear cells. Cord blood mononuclear cells from randomly chosen healthy newborns were co-cultured with the oligosaccharide samples. By means of flow cytometry, intracellular cytokine production (d 20) and surface marker expression of T cells (d 5) were measured. In vitro-induced Ig levels were quantified nephelometrically (total IgG1) and by ELISA (total IgE) in the supernatant of cell cultures. The acidic oligosaccharide fraction increased the percentage of interferon-␥ producing CD3ϩCD4ϩ and CD3ϩCD8ϩ cells (p Ͻ 0.05) and the IL-13 production in CD3ϩCD8ϩ cells (p Ͻ 0.05). In acidic oligosaccharide cultures, CD25ϩ expression on CD3ϩCD4ϩ cells was significantly elevated (p Ͻ 0.05). Low-molecular-weight fucoidan induced IL-4 production in CD3ϩCD4ϩ T cells (p Ͻ 0.05) and IL-13 production in CD3ϩCD8ϩ T cells (p Ͻ 0.05), whereas interferon-␥ production remained unaffected in both T-cell populations. Ig production (total IgE and total IgG1) remained unaffected. Human milk-derived oligosaccharides and plant-derived oligosaccharides affect the cytokine production and activation of cord blood derived T cells in vitro. Therefore, oligosaccharides and, in particular, acidic oligosaccharides may influence lymphocyte maturation in breast-fed newborns. The postnatal period is a crucial time for the maturation of the immune system. At birth, T-lymphocytes exhibit a Th2-profile, characterized by a limited ability to produce cytokines. Throughout the first months after birth these Th2-skewed responses are modified into low-level immunity, predominantly expressing Th1-cytokines and IgG-antibodies, particularly of the IgG1 subclass (1,2).Human milk is a biologic fluid containing large amounts of free oligosaccharides. HMOs represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 20 -23 g/L in colostrum and 12-14 g/L in mature milk (3). HMOs are very resistant to enzymatic hydrolysis (4,5), indicating that these oligosaccharides must display essential nonnutritive functions.Throughout the last decade, numerous studies demonstrated the ability of HMOs to inhibit pathogens acting as receptors for microbes (6,7). Only a few reports on direct effects on immune function have been published so far. Human milk oligosaccharide structures like lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNneoT) showed an effect on murine IL-10 production (8). It is further discussed that human milk is involved in the generation of antiinflammatory mediators that suppress Th1-type and inflammatory responses in mice (9). 0031-3998/04/5604-0536 PEDIATRIC RES...

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Urinary excretion of lactose and oligosaccharides in preterm infants fed human milk or infant formula

Cited by 131 publications

References 27 publications

Investigations of the in Vitro Transport of Human Milk Oligosaccharides by a Caco-2 Monolayer Using a Novel High Performance Liquid Chromatography-Mass Spectrometry Technique

Investigations of the in Vitro Transport of Human Milk Oligosaccharides by a Caco-2 Monolayer Using a Novel High Performance Liquid Chromatography-Mass Spectrometry Technique

Session 1: Feeding and infant development Breast-feeding and immune function

Human Milk–Derived Oligosaccharides and Plant-Derived Oligosaccharides Stimulate Cytokine Production of Cord Blood T-Cells In Vitro

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