title: Pretreatment but not treatment with probiotics abolishes mouse intestinal barrier dysfunction in acute pancreatitis.
abstract: BACKGROUND
  Intestinal barrier failure during acute pancreatitis (AP) is associated with translocation of luminal bacteria, resulting in infectious complications. We examined the effects of multispecies probiotics on the intestinal barrier impairment in a murine model of AP.
  
  
  METHODS
  Mice were injected with cerulein to induce AP and were sacrificed 11 (early AP) or 72 hours (late AP) after start of induction. AP and associated systemic effects were confirmed by histology of pancreas and lung. Animals received daily probiotics starting 2 days prior to AP induction (pretreatment) or at the moment of AP induction (treatment). Mucosal barrier function of the distal ileum was assessed in Ussing chambers by measurement of the epithelial electrical resistance and the permeability to Na-fluorescein.
  
  
  RESULTS
  Histological analysis revealed pancreatic injury in both phases of AP, and lung damage in the early phase. Epithelial resistance of the ileum was reduced and permeability increased in both phases of AP, indicating impairment of the intestinal barrier. Pretreatment had no effect on resistance or permeability in the early phase of AP. In the late phase of AP, pretreatment but not treatment abolished the AP induced resistance decrease and permeability increase. Administration of probiotics as such (ie, without induction of AP) had no effect on intestinal barrier function.
  
  
  CONCLUSIONS
  Pretreatment with multispecies probiotics for 2 days abolishes intestinal barrier dysfunction in the late phase of AP, while treatment does not. The effectiveness of probiotics in this model depends on the timing of administration. Clinical trials with probiotics should seek conditions where treatment can be started prior to onset of disease or elective surgical intervention.
authors.affiliation: Gastrointestinal Research Unit, Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jakub W
authors.initials: JW
authors.lastname: Rychter
authors.forename: L Paul
authors.initials: LP
authors.lastname: van Minnen
authors.forename: André
authors.initials: A
authors.lastname: Verheem
authors.forename: Harro M
authors.initials: HM
authors.lastname: Timmerman
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Hein G
authors.initials: HG
authors.lastname: Gooszen
authors.forename: Louis M A
authors.initials: LM
authors.lastname: Akkermans
authors.forename: Alfons B A
authors.initials: AB
authors.lastname: Kroese
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D001644:Bifidobacterium; D002108:Ceruletide; D007077:Ileal Diseases / Q000209:etiology / Q000517:prevention & control*; D007779:Lactobacillus acidophilus; D007780:Lacticaseibacillus casei; D013294:Lactococcus lactis; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000473:pathology; D019936:Probiotics / Q000008:administration & dosage*
chemical_list: D002108:Ceruletide