title: Evaluation of the anti-adhesive effect of milk fat globule membrane glycoproteins on Helicobacter pylori in the human NCI-N87 cell line and C57BL/6 mouse model.
abstract: BACKGROUND
  The interest in non-antibiotic therapies for Helicobacter pylori infections in man has considerably grown because increasing numbers of antibiotic-resistant strains are being reported. Intervention at the stage of bacterial attachment to the gastric mucosa could be an approach to improve the control/eradication rate of this infection.
  
  
  METHODS
  Fractions of purified milk fat globule membrane glycoproteins were tested in vitro for their cytotoxic and direct antibacterial effect. The anti-adhesive effect on H. pylori was determined first in a cell model using the mucus-producing gastric epithelial cell line NCI-N87 and next in the C57BL/6 mouse model after dosing at 400 mg/kg protein once or twice daily from day -2 to day 4 post-infection. Bacterial loads were determined by using quantitative real-time PCR and the standard plate count method.
  
  
  RESULTS
  The milk fat globule membrane fractions did not show in vitro cytotoxicity, and a marginal antibacterial effect was demonstrated for defatted milk fat globule membrane at 256 μg/mL. In the anti-adhesion assay, the results varied from 56.0 ± 5.3% inhibition for 0.3% crude milk fat globule membrane to 79.3 ± 3.5% for defatted milk fat globule membrane. Quite surprisingly, in vivo administration of the same milk fat globule membrane fractions did not confirm the anti-adhesive effects and even caused an increase in bacterial load in the stomach.
  
  
  CONCLUSIONS
  The promising anti-adhesion in vitro results could not be confirmed in the mouse model, even after the highest attainable exposure. It is concluded that raw or defatted milk fat globule membrane fractions do not have any prophylactic or therapeutic potential against Helicobacter infection.
authors: Laboratory of Microbiology, Parasitology, and Hygiene-LMPH, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
authors: Tessa
authors: T
authors: Horemans
authors: Monique
authors: M
authors: Kerstens
authors: Sofie
authors: S
authors: Clais
authors: Karin
authors: K
authors: Struijs
authors: Pieter
authors: P
authors: van den Abbeele
authors: Tim
authors: T
authors: Van Assche
authors: Louis
authors: L
authors: Maes
authors: Paul
authors: P
authors: Cos
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology; D006017:Glycolipids / Q000008:administration & dosage / Q000494:pharmacology*; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D066292:Lipid Droplets; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D006017:Glycolipids; D006023:Glycoproteins; C110367:milk fat globule