A mixture of neutral short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) has been shown to reduce the incidence of atopic dermatitis (AD) and infectious episodes during the first 6 mo of life. This dual protection occurred through the intervention period. The present study evaluated if these protective effects were lasting beyond the intervention period. In a prospective, randomized, double-blind, placebo-controlled design, healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, blind follow-up continued until 2 y of life. Primary endpoints were cumulative incidence of allergic manifestations. Secondary endpoints were number of infectious episodes and growth. Of 152 participants, 134 infants (68 in placebo, 66 in intervention group) completed the follow-up. During this period, infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations. Cumulative incidences for AD, recurrent wheezing, and allergic urticaria were higher in the placebo group, (27.9, 20.6, and 10.3%, respectively) than in the intervention group (13.6, 7.6, and 1.5%) (P < 0.05). Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections (P < 0.01), fever episodes (P < 0.00001), and fewer antibiotic prescriptions (P < 0.05). Growth was normal and similar in both groups. Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections. The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action.

Prebiotic oligosaccharides are present in breast milk and evidence is pointing toward immunomodulatory properties of the acidic fraction. Recently, prebiotic supplements of infant formula [short-chain galacto (scGOS)-, long-chain fructo (lcFOS)-oligosaccharides] showed preventive effects on atopic disease development. We aimed to define the direct immunologic effects of these oligosaccharides and of human (aHMOS) and cows' milk (aCMOS) acidic oligosaccharides and to investigate the systemic uptake of prebiotic supplements of infant formula and a specific pectin-derived acidic oligosaccharide hydrolysate (pAOS) in vitro. After assurance of LPS-free conditions (limulus assay, toll like receptor-2, -4 transfected human embryonic kidney-cells), in vitro-transfer through a CaCo-2 cell monolayer was measured using high-pH anion exchange chromatography with pulsed amperometric detection. Direct effects on proliferation, cytokine-induction of cord blood mononuclear cells and modulation of allergen-specific CD4+ T-cell cytokine profiles from allergic and non-allergic individuals were investigated. Transfer of scGOS/lcFOS and pAOS in-vitro was detected with a rate of transfer of 4-14%, depending on the molecular size and structure. AHMOS induced IFN-γ and IL-10 but not the Th-2 cytokine IL-13 at physiologic concentrations (10-100 μg/ml) in cord blood, whereas aCMOS did not induce any of these cytokines. AHMOS significantly suppressed Th-2 type cytokine-production by Ara h1-specific CD4+ T cells (CFSE(low) CD3(+) CD4(+) cells) from peanut allergic patients. In conclusion, human milk-derived acidic oligosaccharides may modulate postnatal allergen-specific immune responses by the suppression of Th-2-type responses in atopy-prone individuals. Moreover, there is in vitro evidence for epithelial transport of prebiotic oligosaccharides.

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...

To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer‐related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty‐eight women, who had been treated for cancer were randomly assigned to either a group performing exercise of low‐to‐moderate intensity (LMIE; n = 14) or a group performing high‐intensity interval training (HIIT; n = 14) as part of a 3‐week multimodal rehabilitation program. No adverse events related to the exercise were reported. Work economy improved following both HIIT and LMIE, with improved peak oxygen uptake following LMIE. HIIT reduced mean total body fat mass with no change in body mass, muscle or fat‐free mass (best P < 0.06). LMIE increased muscle and total fat‐free body mass. Total energy expenditure (P = 0.45) did not change between the groups, whereas both improved quality of life to a similar high extent and lessened cancer‐related fatigue. This randomized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects. Here, HIIT and LMIE both improved work economy, quality of life and cancer‐related fatigue, body composition or energy expenditure. Since the outcomes were similar, but HIIT takes less time, this may be a time‐efficient strategy for improving certain aspects of the health of female cancer survivors.

The data indicate that an individual, according to their preferences, and physical-resource-adapted exercise program has a more sustainable impact on the physical activity level in breast cancer patients than the usual care. It is suggested that the rehabilitation program should be personalized for all breast cancer patients.