title: Harvesting the benefits of biofilms: A novel probiotic delivery system for the prevention of necrotizing enterocolitis.
abstract: OBJECTIVE
  Probiotics reduce the incidence of necrotizing enterocolitis (NEC) albeit only when administered at high frequency (at least daily). We have developed a novel probiotic delivery system in which probiotics are grown as a biofilm on microspheres, allowing enhanced efficacy with only a single treatment.
  
  
  METHODS
  Neonatal rats were subjected to experimental NEC. Pups received a single enteral dose of: (1) vehicle only, (2) unloaded microspheres, (3) MRS (broth)-loaded microspheres, (4) Lactobacillus reuteri, (5) L. reuteri grown on unloaded microspheres, or (6) L. reuteri grown on MRS-loaded microspheres. Intestinal injury was graded histologically and intestinal permeability determined by serum levels of enterally administered fluorescein isothiocyanate-labeled dextran.
  
  
  RESULTS
  69% of untreated pups developed NEC, whereas 32% of pups treated with L. reuteri grown as a biofilm on unloaded microspheres (p=0.009) and 33% of pups treated with L. reuteri grown as a biofilm on MRS-loaded microspheres (p=0.005) developed NEC. No other group had a significant reduction in NEC. Furthermore, pups treated with L. reuteri grown as a biofilm had significantly reduced intestinal permeability.
  
  
  CONCLUSIONS
  A single dose of Lactobacillus biofilm grown on biocompatible microspheres significantly reduces NEC incidence and severity. This novel probiotic delivery system may be beneficial in the prevention of NEC in the future.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Olson
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Rager
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Navarro
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mashburn-Warren
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH. Electronic address: Gail.Besner@NationwideChildrens.org.
authors.forename: Gail E
authors.initials: GE
authors.lastname: Besner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018441:Biofilms; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D007422:Intestines / Q000473:pathology; D052200:Limosilactobacillus reuteri; D008863:Microspheres; D019936:Probiotics / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Dextranomer microspheres; Lactobacillus reuteri; Necrotizing enterocolitis; Probiotics; Sephadex