title: Gut microbial colonisation in premature neonates predicts neonatal sepsis.
abstract: BACKGROUND
  Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome.
  
  
  METHODS
  Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis.
  
  
  RESULTS
  Six neonates were 24-27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella.
  
  
  CONCLUSIONS
  In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a 'healthy microbiome' present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates.
authors.affiliation: Department of Pediatrics, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03753, USA. juliette.c.madan@hitchcock.org
authors.forename: Juliette C
authors.initials: JC
authors.lastname: Madan
authors.forename: Richard Cowper
authors.initials: RC
authors.lastname: Salari
authors.forename: Deepti
authors.initials: D
authors.lastname: Saxena
authors.forename: Lisa
authors.initials: L
authors.lastname: Davidson
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Sogin
authors.forename: James A
authors.initials: JA
authors.lastname: Foster
authors.forename: William H
authors.initials: WH
authors.lastname: Edwards
authors.forename: Paul
authors.initials: P
authors.lastname: Palumbo
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hibberd
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018988:Bacterial Translocation; D001483:Base Sequence; D015169:Colony Count, Microbial; D004755:Enterobacteriaceae / Q000235:genetics / Q000302:isolation & purification; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000382:microbiology*; D019102:Infant, Very Low Birth Weight; D008137:Longitudinal Studies; D008470:Meconium / Q000382:microbiology; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D012307:Risk Factors; D018805:Sepsis / Q000382:microbiology*; D013210:Staphylococcus / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D012333:RNA, Messenger