Prebiotic oligosaccharides and 2’-fucosyllactose improve host microbe interaction in a murine vaccination model. mouse gut metagenome

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 (pConclusion: 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.