Denise Ney, PhD

Slide of the Week: Denise Ney, PhD

Title:  Glycomacropeptide (GMP) is a bioactive peptide released from casein in milk during cheesemaking that contains no aromatic amino acids. GMP is isolated for use in medical foods for the management of phenylketonuria (PKU) based on research conducted in Dr. Denise Ney’s laboratory at UW-Madison. GMP is an acidic, highly polar peptide that is hydrophilic and heat stable with a theoretical molecular mass between 7-11 kDa.    The extensive glycosylation of GMP at threonine residues results in beneficial prebiotic properties including increased levels of short chain fatty acids in colon and reduced inflammation.  Beyond PKU GMP also has application to the management of human colitis and Crohn’s disease.

Citation:  Sawin EA, De Wolfe TJ, Aktas B, Stroup BM, Murali SG and Ney DM. (2015). Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice.  American Journal of PhysiologyGastrointestinal and Liver Physiology, 309:G590-G601,  DOI 10.1152/ajpgi.00211,2015.


Background: 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.

Objective: To determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations, short chain fatty acids (SCFA) and immune responses.

Methods: Weanling PKU (Pahenu2) and wild type (WT) C57Bl/6 mice were fed isoenergetic AA, GMP or casein diets for 8 weeks.  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 GC, plasma cytokines using a Bio-Plex Pro assay, and splenocyte T cell populations using flow cytometry.

Results: 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-gamma (IFN-γ) was significantly reduced in mice fed GMP compared to casein. Plasma concentrations of IFN-γ, TNF-α, IL-1β and IL-2 were reduced in mice fed GMP. Conclusions: GMP is a prebiotic based on reduction in Desulfovibrio, increased SCFA and lower indices 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.

About the lab: The Ney research group has conducted studies in individuals with phenylketonuria (PKU) that establishes the acceptability and safety of foods made with the whey protein, glycomacropeptide, in the nutritional management PKU. PKU is a genetic disorder caused by deficiency of the hepatic enzyme phenylalanine hydroxylase that converts the essential amino acid phenylalanine to tyrosine. The Waisman Biochemical Genetics Clinics follows over 160 clients with PKU. To prevent brain damage and cognitive impairment those with PKU must follow a lifelong, low-phenylalanine diet that is restricted in natural foods and requires ingestion of a bitter tasting amino acid formula. Glycomacropeptide is uniquely suited to the PKU diet because it is the only known dietary proteins that contains only trace amounts of phenylalanine. Low-phenylalanine food products made from GMP provide a palatable and acceptable alternative to the amino acid formulas currently required in the PKU diet.

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