Prebiotic oligosaccharides: <i>In vitro</i> evidence for gastrointestinal epithelial transfer and immunomodulatory properties

Abstract

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.