title: Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice.
abstract: Glycomacropeptide (GMP) is a 64-amino acid (AA) glycophosphopeptide with application to the nutritional management of phenylketonuria (PKU), obesity, and inflammatory bowel disease (IBD). GMP is a putative prebiotic based on extensive glycosylation with sialic acid, galactose, and galactosamine. Our objective was to determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations, short-chain fatty acids (SCFA), and immune responses. Weanling PKU (Pah(enu2)) and wild-type (WT) C57Bl/6 mice were fed isoenergetic AA, GMP, or casein diets for 8 wk. The cecal content and feces were collected for microbial DNA extraction to perform 16S microbiota analysis by Ion Torrent PGM sequencing. SCFA were determined by gas chromatography, plasma cytokines via a Bio-Plex Pro assay, and splenocyte T cell populations by flow cytometry. Changes in cecal and fecal microbiota are primarily diet dependent. The GMP diet resulted in a reduction from 30-35 to 7% in Proteobacteria, genera Desulfovibrio, in both WT and PKU mice with genotype-dependent changes in Bacteroidetes or Firmicutes. Cecal concentrations of the SCFA acetate, propionate, and butyrate were increased with GMP. The percentage of stimulated spleen cells producing interferon-γ (IFN-γ) was significantly reduced in mice fed GMP compared with casein. In summary, plasma concentrations of IFN-γ, TNF-α, IL-1β, and IL-2 were reduced in mice fed GMP. GMP is a prebiotic based on reduction in Desulfovibrio, increased SCFA, and lower indexes of inflammation compared with casein and AA diets in mice. Functional foods made with GMP may be beneficial in the management of PKU, obesity, and IBD.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Sawin
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: De Wolfe
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Busra
authors.initials: B
authors.lastname: Aktas
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Stroup
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and.
authors.forename: Sangita G
authors.initials: SG
authors.lastname: Murali
authors.affiliation: Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: James L
authors.initials: JL
authors.lastname: Steele
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and ney@nutrisci.wisc.edu.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ney
mesh_terms: D000818:Animals; D002364:Caseins / Q000008:administration & dosage*; D002432:Cecum / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003901:Desulfovibrio / Q000187:drug effects*; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D010661:Phenylketonurias / Q000188:drug therapy* / Q000378:metabolism; D056692:Prebiotics / Q000008:administration & dosage*
chemical_list: D002364:Caseins; D016207:Cytokines; D005232:Fatty Acids, Volatile; D010446:Peptide Fragments; D056692:Prebiotics; C065989:caseinomacropeptide
keywords: cytokines; inflammatory bowel disease; phenylketonuria; sialic acid; sulfate reducing bacteria