title: Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs.
abstract: Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis, while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and delay gut bacterial colonization and thereby protect preterm neonates against both NEC and bacteremia in the immediate postnatal period. Preterm pigs were given formula and administered saline (CON) or broad-spectrum antibiotics orally (ORA) or systemically (SYS) for 5 d after birth. Temporal changes in blood parameters and bacterial composition in the intestine, blood and immune organs were analyzed. Newborn preterm pigs had few blood neutrophils and a high frequency of progenitor cells. Neutrophils gradually matured after preterm birth with increasing CD14 and decreasing CD172a expressions. Preterm neutrophil and monocyte TLR2 expression and TLR2-mediated blood cytokine responses were low relative to adults. ORA pigs showed enhanced blood neutrophil maturation with reduced cell size and CD172a expression. Only ORA pigs, but not SYS pigs, were protected from a high density of gut Gram-positive bacteria, high gut permeability, Gram-positive bacteremia and NEC. Neonatal oral antibiotics may benefit mucosal and systemic immunity via delayed gut colonization and enhanced blood neutrophil maturation just after preterm birth.
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Duc Ninh
authors.initials: DN
authors.lastname: Nguyen
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Fuglsang
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, 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, Frederiksberg, Denmark.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Shamrulazhar B S
authors.initials: SB
authors.lastname: Kamal
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Pors
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Pernille L
authors.initials: PL
authors.lastname: Gammelgaard
authors.affiliation: Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Nielsen
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Harvard, MA, USA.
authors.forename: Ofer
authors.initials: O
authors.lastname: Levy
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiær
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark pts@sund.ku.dk.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D016470:Bacteremia / Q000188:drug therapy* / Q000276:immunology; D001773:Blood Cells / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D013552:Swine; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D051195:Toll-Like Receptor 2
keywords: Antibiotics; TLR2; neonatal immunity; neutrophils; preterm pig