title: Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs.
abstract: Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90-92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n = 16-17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59-63%) in CON and PAR pigs (P < 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P < 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P < 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formula-fed preterm neonates.
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Malene M
authors.initials: MM
authors.lastname: Birck
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Duc Ninh
authors.initials: DN
authors.lastname: Nguyen
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Malene S
authors.initials: MS
authors.lastname: Cilieborg
authors.affiliation: Department of Food Science, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Shamrulazhar S
authors.initials: SS
authors.lastname: Kamal
authors.affiliation: Department of Food Science, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Damborg
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: John E
authors.initials: JE
authors.lastname: Olsen
authors.affiliation: Department of Animal Science, Aarhus University, Arrhus, Denmark;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lauridsen
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark; thomas.thymann@sund.ku.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000517:prevention & control; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D041943:Infant Formula / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial / Q000379:methods; D007422:Intestines / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D007441:Intubation, Gastrointestinal / Q000379:methods; D008795:Metronidazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011247:Pregnancy; D047928:Premature Birth; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008795:Metronidazole; D000667:Ampicillin
keywords: antibiotics; enteral antibiotics; necrotizing enterocolitis; preterm pig