title: Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis.
abstract: Neonatal necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. Oral administration of probiotics has been suggested as a promising strategy for prevention of NEC. However, little is known about the mechanism(s) of probiotic-mediated protection against NEC. The aim of this study was to evaluate the effects of Bifidobacterium bifidum treatment on development of NEC, cytokine regulation, and intestinal integrity in a rat model of NEC. Premature rats were divided into three groups: dam fed (DF), hand fed with formula (NEC), or hand fed with formula supplemented with 5 x 10(6) CFU B. bifidum per day (B. bifidum). All groups were exposed to asphyxia and cold stress to develop NEC. Intestinal injury, mucin and trefoil factor 3 (Tff3) production, cytokine levels, and composition of tight junction (TJ) and adherens junction (AJ) proteins were evaluated in the terminal ileum. B. bifidum decreased the incidence of NEC from 57 to 17%. Increased levels of IL-6, mucin-3, and Tff3 in the ileum of NEC rats was normalized in B. bifidum treated rats. Reduced mucin-2 production in the NEC rats was not affected by B. bifidum. Administration of B. bifidum normalized the expression and localization of TJ and AJ proteins in the ileum compared with animals with NEC. In conclusion, administration of B. bifidum protects against NEC in the neonatal rat model. This protective effect is associated with reduction of inflammatory reaction in the ileum, regulation of main components of mucus layer, and improvement of intestinal integrity.
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, Arizona 85724-5073, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Khailova
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorak
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Arganbright
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Halpern
authors.forename: Toshi
authors.initials: T
authors.lastname: Kinouchi
authors.forename: Masako
authors.initials: M
authors.lastname: Yajima
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000150:complications; D001644:Bifidobacterium; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D062465:Claudin-3; D003080:Cold Temperature; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D020895:Enterocytes / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D015994:Incidence; D007378:Interleukins / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D055263:Mucin-3 / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D019936:Probiotics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D019108:Tight Junctions / Q000378:metabolism; D000071165:Trefoil Factor-3; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015820:Cadherins; D051177:Catenins; D062465:Claudin-3; C568124:Cldn3 protein, rat; D007378:Interleukins; D008565:Membrane Proteins; C524628:Muc2 protein, rat; C524651:Muc3 protein, rat; D055262:Mucin-2; D055263:Mucin-3; D009479:Neuropeptides; D062793:Occludin; C568987:Ocln protein, rat; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3; D014409:Tumor Necrosis Factor-alpha