Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study

Hvas, Christian Lodberg; Dige, Anders; Bendix, Mia; Wernlund, Pernille Glahn; Christensen, Lisbet Ambrosius; Dahlerup, Jens Frederik; Agnholt, Jørgen

doi:10.1111/eci.12634

Cited by 28 publications

(25 citation statements)

References 40 publications

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“…This highly glycosylated 64-amino acid peptide presents an average molecular weight of 7.5 kDa [ 22 ]. It is considered safe for human use and is not immunogenic regardless of the administration route [ 23 , 24 ]. GMP is free from phenylalanine residues, which allows it to be used as a protein-based ingredient in the formulation of food products for the nutrition of phenylketonuria patients [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

et al. 2020

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Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1β and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response.

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Section: Introductionmentioning

confidence: 99%

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

et al. 2020

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“…This study indicates that GMP has potential as a bioactive ingredient which could assist in improving the gastrointestinal health of individuals. Indeed, recently GMP has shown promise as a nutritional therapy in patients with active distal ulcerative colitis [ 68 ]. Moreover, methods for producing GMP based on its glycosylation and the effect of its glycosylation on the peptide’s techno-functional properties have been documented [ 69 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

Glycomacropeptide Reduces Intestinal Epithelial Cell Barrier Dysfunction and Adhesion of Entero-Hemorrhagic and Entero-Pathogenic Escherichia coli in Vitro

Feeney

Ryan

Kilcoyne

et al. 2017

Foods

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In recent years, the potential of glycosylated food components to positively influence health has received considerable attention. Milk is a rich source of biologically active glycoconjugates which are associated with antimicrobial, immunomodulatory, anti-adhesion, anti-inflammatory and prebiotic properties. Glycomacropeptide (GMP) is the C-terminal portion of kappa-casein that is released from whey during cheese-making by the action of chymosin. Many of the biological properties associated with GMP, such as anti-adhesion, have been linked with the carbohydrate portion of the protein. In this study, we investigated the ability of GMP to inhibit the adhesion of a variety of pathogenic Escherichia coli strains to HT-29 and Caco-2 intestinal cell lines, given the importance of E. coli in causing bacterial gastroenteritis. GMP significantly reduced pathogen adhesion, albeit with a high degree of species specificity toward enteropathogenic E. coli (EPEC) strains O125:H32 and O111:H2 and enterohemorrhagic E. coli (EHEC) strain 12900 O157:H7. The anti-adhesive effect resulted from the interaction of GMP with the E. coli cells and was also dependent on GMP concentration. Pre-incubation of intestinal Caco-2 cells with GMP reduced pathogen translocation as represented by a decrease in transepithelial electrical resistance (TEER). Thus, GMP is an effective in-vitro inhibitor of adhesion and epithelial injury caused by E. coli and may have potential as a biofunctional ingredient in foods to improve gastrointestinal health.

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“…A pilot study conducted in patients with ulcerative colitis, observed anti-inflammatory clinical effects of CGMP after four weeks. (40) Studies of dietary-induced CRP changes reported CRP decreases after two to three weeks. (41,42) Regarding the impact of dietary intervention on microbiota composition, studies found changes after five days to four Accepted manuscript amino acids, arginine, cysteine, and histidine.…”

Section: Methodsmentioning

confidence: 99%

Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial

et al. 2020

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Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that a daily oral CGMP intake would reduce high-sensitive C-reactive protein in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a four-week intervention of either 25 grams of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, either with regard to high-sensitive C-reactive protein, or faecal calprotectin level, faecal microbiota composition or faecal short-chain fatty acid content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 grams of CGMP during four weeks was safe, well tolerated, had acceptable palatability, and was without any effects on body weight.

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Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study

Abstract: The addition of CGMP as a nutritional therapy to standard treatment was safe and accepted by patients with active distal UC. The disease-modifying effect of CGMP was similar to that of the mesalamine dose escalation.

Cited by 28 publications

References 40 publications

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

Glycomacropeptide Reduces Intestinal Epithelial Cell Barrier Dysfunction and Adhesion of Entero-Hemorrhagic and Entero-Pathogenic Escherichia coli in Vitro

Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial

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