Fermentation generated human milk oligosaccharides promote a TH1 response in a murine influenza vaccination model

Objectives and Study: The intestinal flora of breast-fed infants is dominated by Bifidobacteria, whereas the intestinal flora of bottle-fed infants consists of lower numbers of Bifidobacteria, but higher levels of Enterobacteria and other pathogenic germs. Oligosaccharides are a major constituent of human milk that demonstrated to promote the growth and activity of beneficial bacteria, mainly Bifidobacteria and Lactobacilli. However, the mechanism by which oligosaccharides exert their effects remains to be elucidated. To further study the mechanism by which oligosaccharides can modulate systemic immune responses, the present study examined by fermentation produced oligosaccharides that are identical to Human Milk Oligosaccharides (HMO) in a murine influenza vaccination model. Methods: C57BL/6 mice received a control diet or a diet supplemented with different by fermentation generated HMO at a dietary dose of 1%. The mice were vaccinated twice with Influvac and the response was determined by the measurement of delayed type hypersensitivity (DTH) reaction in the ear pinnae. In addition, antigen-specific antibody and immunoglobulin-free light chain concentrations in serum, ex vivo induced splenic proliferation, the level of regulatory T cells and NK cells, and the functional activity of these NK cells were determined. Results: The by fermentation generated HMO significantly enhanced the DTH responses. Supplementation with HMO reduced the level of regulatory T cells, whereas the percentage and activity of splenic NK cells increased. Furthermore, the level of antigen-specific IgG1 was significantly increased in mice fed with HMO. Interestingly, one HMO was able to significantly increase the serum concentration of free light chain, whereas others did not alter any differences. In addition, syngergistic effects on the DTH response could be achieved by combination of these HMO with oligosaccharides from plant- and animal sources. No significant changes were detected on splenocyte proliferation. Conclusion: These data suggest that HMO can stimulate the adaptive immune response into a Th1 direction, and therefore might provide an opportunity to inhibit infections and Th2-related immune disorders in humans.