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

Abstract

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...

Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides

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Intestinal fermentation of lactose and prebiotic lactose derivatives, including human milk oligosaccharides

“…There is striking evidence that HMOs are potent inhibitors of bacterial and viral adhesion to epithelial surfaces (Kunz et al, 2000;Martin, Martin-Sosa, & Hueso, 2002), an initial stage of infective processes, because the HMOs mimic the glycans on epithelial receptors (see review by Hickey, in press). HMOs have also been shown to have immunomodulatory properties (Bode, 2009;Eiwegger et al, 2004Eiwegger et al, , 2010. Furthermore, they have been implicated to play an important role in brain development (Kunz et al, 2000).…”

Clinical applications of bioactive milk components

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