Glycomacropeptide Shows Prebiotic and Immune Modulating Properties in Phenylketonuria and Wild Type Mice

Abstract

BackgroundGlycomacropeptide (GMP) is a 64 amino acid (AA) glycophosphopeptide with application to the nutritional management of phenylketonuria (PKU), obesity and intestinal disorders. GMP is a putative prebiotic based on its carbohydrate content including sialic acid.ObjectiveTo determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations and immune responses in C57Bl/6 mice.MethodsWeanling PKU (Pahenu2) and wild type (WT) mice were fed isoenergetic AA, GMP or casein diets for 8 weeks. The cecum content and feces were collected for microbial DNA extraction to perform 16S microbiota analysis by Ion Torrent PGM sequencing. Plasma cytokines were determined using a Bio‐Plex Pro assay and splenocyte T cell populations were assessed using flow cytometry.ResultsPairwise comparison suggests that changes in cecal microbiota are primarily diet dependent. The GMP diet resulted in a significant reduction in Proteobacteria, genera Desulfovibrio, in both WT and PKU mice with genotype‐dependent changes in Bacteroides or Firmicutes. The percentage of stimulated spleen cells producing interferon‐gamma (IF‐γ) was significantly reduced in mice fed GMP compared to casein. Plasma concentrations of IF‐γ and tumor necrosis factor‐α were lowest in mice fed GMP.ConclusionsGMP is a prebiotic based on modulation of the intestinal microbiota compared with casein and AA diets in mice. The shift in microbial populations with GMP appears to be beneficial based on lower indices of inflammation with GMP.