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

Abstract

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.

Lectin microarray profiling and monosaccharide analysis of bovine milk immunoglobulin G oligosaccharides during the first 10 days of lactation

“…IgG α-(2→6)linked sialylation is associated with decreased inflammation following Fc receptor binding (Marth & Grewal, 2008). Sialic acid on other milk glycoproteins is thought to play important roles in binding E. coli and Salmonella enteritidis (Feeney, Ryan, Kilcoyne, Joshi, & Hickey, 2017;Nakajima et al, 2005), promoting the growth of the bifidobacteria strains such as Bifidobacterium breve, B. bifidum, and B. infantis (Idota, Kawakami, & Nakajima, 1994), preventing Helicobacter pylori colonization (Wang et al, 2007), inhibiting haemagglutination by the influenza virus (Kawasaki et al, 1993), and promoting calcium-binding properties (Jaques, Brown, Barrett, Brey, & Weltner, 1977).…”

Glycomacropeptide Prevents Iron/Ascorbate-Induced Oxidative Stress, Inflammation and Insulin Sensitivity with an Impact on Lipoprotein Production in Intestinal Caco-2/15 Cells

“…This carbohydrate-containing compound can survive gastric transit without hydrolysis and is absorbed intact into the bloodstream [16,17]. Even if 30 years ago GMP was considered as a source of energy, it now becomes obvious that it has also the potential of modulating various biological processes, including binding of cholera toxin and E. Coli enterotoxins, inhibition of bacterial and viral adhesion, suppression of gastric secretion, and promotion of bifidobacterial growth [18][19][20][21][22]. The anti-inflammatory and immunomodulatory effects of GMP have been reported in rodent models of inflammatory bowel disease [23,24], murine spleen and bone marrow dendritic cells [25,26], as well as in lymphocytes and macrophages [27].…”

Glycomacropeptide: Biological Activities and Uses

“…Besides, it has been reported that GMP generates dose-dependent inhibition of enterotoxigenic E. coli (ETEC) K88 adhesion to ileal mucosa in vitro [12]. Finally, a recent report showed that GMP also prevents the attachment of several strains of EHEC and EPEC to Caco-2 and HT-29 mammalian cells [13]. In this study, it was demonstrated that GMP, beyond inhibiting bacterial adhesion, is able to maintain the structural integrity of tight junctions on Caco-2 monolayers, thus delaying the paracellular translocations of EPEC.…”