title: Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis.
abstract: Whether intestinal barrier disruption precedes or is the consequence of intestinal injury in necrotizing enterocolitis (NEC) remains unknown. Using a neonatal mouse NEC model, we examined the changes in intestinal permeability and specific tight-junction (TJ) proteins preceding NEC and asked whether these changes are prevented by administration of Bifidobacterium infantis, a probiotic known to decrease NEC incidence in humans. Compared with dam-fed controls, pups submitted to the NEC protocol developed i) significantly increased intestinal permeability at 12 and 24 hours (as assessed by 70-kDa fluorescein isothiocyanate-dextran transmucosal flux); ii) occludin and claudin 4 internalization at 12 hours (as assessed by immunofluorescence and low-density membrane fraction immunoblotting); iii) increased claudin 2 expression at 6 hours and decreased claudin 4 and 7 expression at 24 hours; and iv) increased claudin 2 protein at 48 hours. Similar results were seen in human NEC, with claudin 2 protein increased. In mice, administration of B. infantis micro-organisms attenuated increases in intestinal permeability, preserved claudin 4 and occludin localization at TJs, and decreased NEC incidence. Thus, an increase in intestinal permeability precedes NEC and is associated with internalization of claudin 4 and occludin. Administration of B. infantis prevents these changes and reduces NEC incidence. The beneficial effect of B. infantis is, at least in part, due to its TJ and barrier-preserving properties.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Bergmann
authors.forename: Shirley X L
authors.initials: SX
authors.lastname: Liu
authors.forename: Runlan
authors.initials: R
authors.lastname: Tian
authors.forename: Anna
authors.initials: A
authors.lastname: Kushnir
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Li
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Chou
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Weber
authors.forename: Isabelle G
authors.initials: IG
authors.lastname: De Plaen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001644:Bifidobacterium / Q000502:physiology*; D051242:Caveolin 1 / Q000378:metabolism; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004705:Endocytosis; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology*; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D007422:Intestines / Q000382:microbiology* / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D021381:Protein Transport; D013312:Stress, Physiological; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051242:Caveolin 1; D057167:Claudins; D062793:Occludin