title: Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs.
abstract: It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml·kg(-1)·day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 ± 1 vs. 22 ± 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1β and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants.
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark;
authors.forename: René L
authors.initials: RL
authors.lastname: Shen
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark;
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark;
authors.forename: Mette V
authors.initials: MV
authors.lastname: Østergaard
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark; Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark;
authors.forename: Ann Cathrine F
authors.initials: AC
authors.lastname: Støy
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark;
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Krych
authors.affiliation: Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark;
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: Department of Animal Science, Aarhus University, Aarhus, Denmark;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lauridsen
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, Copenhagen, Denmark;
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, Copenhagen, Denmark;
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, Texas; USDA/ARS Children's Nutrition Research Center, Houston, Texas; and.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark; Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark pts@sund.ku.dk.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001903:Bottle Feeding; D002417:Cattle; D003126:Colostrum / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D020345:Enterocolitis, Necrotizing / Q000662:veterinary*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D011247:Pregnancy; D013552:Swine
chemical_list: D000596:Amino Acids; D016207:Cytokines; D053767:Glucagon-Like Peptide 2; D005749:Gastric Inhibitory Polypeptide
keywords: colostrum; enteral nutrition; formula; necrotizing enterocolitis; preterms