Prebiotic oligosaccharides and 2'-fucosyllactose improve host microbe interaction in a murine vaccination model

Background: Human milk oligosaccharides (HMOS) play a critical role in the immunological development of breastfed infants. HMOS consist of short-chain (sc) and long-chain (lc) oligosaccharides in a 9:1 ratio. 2'-Fucosyllactose (2'FL) is one of the most abundant HMOS that has been reported to improve the vaccine responsiveness. Therefore, a combination of 2'FL with prebiotic scGalacto-oligosaccharide (scGOS) and lcFructo-oligosaccharide (lcFOS) (9/1) was designed to resemble the composition and function of authentic HMOS.Aim: To investigate the effect of 2'FL/scGOS/lcFOS on microbiota composition and vaccine-specific immune responses in a murine influenza vaccination model, and elucidate mechanisms involved.Methods: Dietary intervention was provided to the C57BL/6 mice two weeks prior to vaccination with influvacc until the end of the experiment. Immune responsiveness was determined by measuring Vaccine-specific delayed-type hypersensitivity (DTH), serum antibody levels, and immune cell populations in the mesenteric lymph node (MLN). In addition, microbiota composition and its metabolites short chain fatty acids (SCFAs) in cecum content and feces were measured using 16S rRNA sequencing and Gas Chromatography, respectively.Results: In mice receiving 2'FL/scGOS/lcFOS diet, increased influenza vaccine-specific DTH response was detected (p<0.01) as well as elevated IgG1 and IgG2a levels were detected compared to control mice. In the MLN of mice receiving 2'FL/scGOS/lcFOS diet a significant (p<0.05) activation of CD103-DCs, and increased percentages of activated B-cell, Tregs and Th1 cells was detected as compared to mice receiving control diets. Interestingly the increased levels of cecal short chain fatty acids (SCFAs) was significantly correlated with both the DTH responses as well as the humoral response. Furthermore, significant correlations were detected between specific genera and vaccine-specific responses which supports the finding that addition of 2'FL/scGOS/lcFOS to the diet significantly alters microbial development and (a and b) diversity in mice.Conclusion: Dietary intervention with prebiotic 2'FL/scGOS/lcFOS improves the immune response as measured by influenza vaccine responses in mice. These changes correlate to the microbiota composition and are suggestive for improvement of host microbial interaction starting at the mucosal surface.