title: A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium: Results of a Prospective Study.
abstract: BACKGROUND
  Anomalous intestinal microbiota development is supposedly associated with development of necrotizing enterocolitis (NEC). Our aim in this study was to identify the intestinal microbiota of patients at risk for NEC.
  
  
  METHODS
  In a prospective trial that investigated prognostic factors for development of NEC in high-risk neonates (NTR4153), 11 NEC cases were gestational age/birthweight matched with controls (ratio of 1:2). Feces were collected twice a week. We used the first feces sample of each patient (meconium), as well as the last 2 feces samples prior to development of NEC. DNA was extracted, and the bacterial 16S rRNA genes were analyzed on a MiSeq sequencer.
  
  
  RESULTS
  The presence and abundance of Clostridium perfringens (8.4%) and Bacteroides dorei (0.9%) in meconium were increased in neonates who developed NEC compared with controls (0.1% and 0.2%; both species, P < .001). In post-meconium samples, the abundance of staphylococci became negatively associated with NEC development (P = .1 and P = .01 for consecutive samples); Clostridium perfringens continued to be more prevalent in NEC cases. Early enteral feeding and, in particular, breast milk were correlated with an increase in lactate-producing bacilli in post-meconium samples (ρ = -0.45; P = .004).
  
  
  CONCLUSIONS
  A NEC-associated gut microbiota can be identified in meconium samples; C. perfringens continues to be associated with NEC from the first meconium till just before NEC onset. In contrast, in post-meconium, increased numbers of staphylococci were negatively associated with NEC. These findings suggest causality but this causality should be verified in trials of induced infection in animals, targeted antibiotics, and/or probiotics.
  
  
  BACKGROUND
  CALIFORNIA trial, registered under trial number NTR4153 in the Dutch Trial Registry.
authors.affiliation: Department of Pediatric Surgery.|Department of Medical Microbiology.
authors.forename: Fardou H
authors.initials: FH
authors.lastname: Heida
authors.affiliation: Department of Pediatric Surgery.
authors.forename: Anne G J F
authors.initials: AGJF
authors.lastname: van Zoonen
authors.affiliation: Department of Pediatric Surgery.
authors.forename: Jan B F
authors.initials: JBF
authors.lastname: Hulscher
authors.affiliation: Department of Pediatric Surgery.
authors.forename: Bastiaan J C
authors.initials: BJC
authors.lastname: Te Kiefte
authors.affiliation: Department of Pediatric Surgery.
authors.forename: Rianne
authors.initials: R
authors.lastname: Wessels
authors.affiliation: Department of Neonatology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Elisabeth M W
authors.initials: EMW
authors.lastname: Kooi
authors.affiliation: Department of Neonatology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Arend F
authors.initials: AF
authors.lastname: Bos
authors.affiliation: Department of Medical Microbiology.
authors.forename: Hermie J M
authors.initials: HJM
authors.lastname: Harmsen
authors.affiliation: Department of Medical Microbiology.
authors.forename: Marcus C
authors.initials: MC
authors.lastname: de Goffau
mesh_terms: D000328:Adult; D002585:Cesarean Section / Q000706:statistics & numerical data; D002821:Chorioamnionitis / Q000453:epidemiology; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology* / Q000382:microbiology* / Q000401:mortality; D008297:Male; D008470:Meconium / Q000382:microbiology*; D011247:Pregnancy; D025341:Principal Component Analysis; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: gut microbiota; microbiome profiling; necrotizing enterocolitis