title: Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.
abstract: Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.
authors.affiliation: Department of Animal Science, University of California, Davis, USA. eamaga@ucdavis.edu.
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Garas
authors.affiliation: Molecular and Developmental Biology Lab, University of Fortaleza, Fortaleza CE, Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Feltrin
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: M Kristina
authors.initials: MK
authors.lastname: Hamilton
authors.affiliation: Department of Animal Science, University of California, Davis, USA. eamaga@ucdavis.edu.
authors.forename: Jill V
authors.initials: JV
authors.lastname: Hagey
authors.affiliation: Department of Animal Science, University of California, Davis, USA. eamaga@ucdavis.edu and Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Murray
authors.affiliation: Molecular and Developmental Biology Lab, University of Fortaleza, Fortaleza CE, Brazil.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Bertolini
authors.affiliation: Molecular and Developmental Biology Lab, University of Fortaleza, Fortaleza CE, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Bertolini
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Raybould
authors.affiliation: Department of Animal Science, University of California, Davis, USA. eamaga@ucdavis.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Maga
mesh_terms: D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007781:Lactoferrin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D044342:Malnutrition / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008892:Milk / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D016753:Interleukin-10; D007781:Lactoferrin