Lactoferrin as a natural regimen for selective decontamination of the digestive tract: recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonates from pathogenic challenge in the gastrointestinal tract

J Infect Dis. 2009 Feb 15;199(4):590-8. doi: 10.1086/596212.

Abstract

Background: Nosocomial infection with antibiotic-resistant strains is a major threat to critical care medicine. Selective decontamination of the digestive tract (SDD) is one of the strategies used to reduce ventilator-associated pneumonia and sepsis in critically ill patients. In the present study, we performed pathogenic challenges of the digestive tract in a transgenic milk-fed animal model to test whether porcine lactoferrin (pLF) is an effective SDD regimen.

Methods: Transgenic mice expressing recombinant pLF in their milk at a mean+/-SD concentration of 120+/-13.6 mg/L during the lactation stage fed normal CD-1 mice pups for 4 weeks. The pups were subsequently challenged with pathogenic Escherichia coli, Staphylococcus aureus, and Candida albicans.

Results: Compared with the control groups fed wild-type (normal) milk, the groups fed pLF-enriched milk demonstrated statistically significant improvements in weight gain; lower bacterial numbers in intestinal fluid, blood, and liver; healthier microvilli in the small intestine; and alveoli in the lungs.

Conclusions: Our results showed that oral administration of pLF-enriched milk to mice led to broad-spectrum antimicrobial activity in the digestive tract and protected the mucosa of the small intestine from injury, implying that pLF can be used as an effective SDD regimen.

MeSH terms

  • Animals
  • Animals, Newborn
  • Bacteremia / microbiology
  • Bacteremia / prevention & control
  • Bacterial Infections / pathology
  • Bacterial Infections / prevention & control*
  • Body Weight
  • Candidiasis / pathology
  • Candidiasis / prevention & control
  • Cytokines / metabolism
  • Escherichia coli Infections / pathology
  • Escherichia coli Infections / prevention & control
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / pathology
  • Immunohistochemistry
  • Intestines / microbiology
  • Intestines / pathology
  • Lactation*
  • Lactoferrin / genetics*
  • Lactoferrin / metabolism*
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Transgenic
  • Milk / chemistry*
  • Polymerase Chain Reaction
  • Recombinant Proteins / metabolism
  • Staphylococcal Infections / pathology
  • Staphylococcal Infections / prevention & control
  • Swine

Substances

  • Cytokines
  • Recombinant Proteins
  • Lactoferrin