title: Antibiotics increase gut metabolism and antioxidant proteins and decrease acute phase response and necrotizing enterocolitis in preterm neonates.
abstract: BACKGROUND
  The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms.
  
  
  RESULTS
  Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased.
  
  
  CONCLUSIONS
  Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Jiang
authors.forename: Michael Ladegaard
authors.initials: ML
authors.lastname: Jensen
authors.forename: Malene Skovsted
authors.initials: MS
authors.lastname: Cilieborg
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Jennifer Man-Fan
authors.initials: JM
authors.lastname: Wan
authors.forename: Wai-Hung
authors.initials: WH
authors.lastname: Sit
authors.forename: George L
authors.initials: GL
authors.lastname: Tipoe
authors.forename: Per Torp
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D020345:Enterocolitis, Necrotizing / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D008871:Microvilli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D047928:Premature Birth / Q000378:metabolism*; D040901:Proteomics; D013552:Swine
chemical_list: D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D000975:Antioxidants