Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis

Ludmila Khailova, Katerina Dvorak, Kelly M. Arganbright, Melissa D Halpern, Toshi Kinouchi, Masako Yajima, Bohuslav Dvorak

Research output: Contribution to journalArticle

111 Citations (Scopus)

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 106 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume297
Issue number5
DOIs
StatePublished - Nov 2009

Fingerprint

Necrotizing Enterocolitis
Ileum
Adherens Junctions
Tight Junctions
Probiotics
Bifidobacterium bifidum
Mucin-3
Mucin-2
Hand
Cytokines
Asphyxia
Mucins
Mucus
Premature Infants
Oral Administration
Interleukin-6
Proteins

Keywords

  • Adherens junctions
  • Intestinal barrier function
  • Mucins
  • Tight junctions

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. / Khailova, Ludmila; Dvorak, Katerina; Arganbright, Kelly M.; Halpern, Melissa D; Kinouchi, Toshi; Yajima, Masako; Dvorak, Bohuslav.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 297, No. 5, 11.2009.

Research output: Contribution to journalArticle

Khailova, Ludmila ; Dvorak, Katerina ; Arganbright, Kelly M. ; Halpern, Melissa D ; Kinouchi, Toshi ; Yajima, Masako ; Dvorak, Bohuslav. / Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2009 ; Vol. 297, No. 5.
@article{29a7aae3e6d042499ef03d006394b573,
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 106 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.",
keywords = "Adherens junctions, Intestinal barrier function, Mucins, Tight junctions",
author = "Ludmila Khailova and Katerina Dvorak and Arganbright, {Kelly M.} and Halpern, {Melissa D} and Toshi Kinouchi and Masako Yajima and Bohuslav Dvorak",
year = "2009",
month = "11",
doi = "10.1152/ajpgi.00141.2009",
language = "English (US)",
volume = "297",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis

AU - Khailova, Ludmila

AU - Dvorak, Katerina

AU - Arganbright, Kelly M.

AU - Halpern, Melissa D

AU - Kinouchi, Toshi

AU - Yajima, Masako

AU - Dvorak, Bohuslav

PY - 2009/11

Y1 - 2009/11

N2 - 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 106 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.

AB - 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 106 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.

KW - Adherens junctions

KW - Intestinal barrier function

KW - Mucins

KW - Tight junctions

UR - http://www.scopus.com/inward/record.url?scp=72249114272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72249114272&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00141.2009

DO - 10.1152/ajpgi.00141.2009

M3 - Article

C2 - 20501441

AN - SCOPUS:72249114272

VL - 297

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 5

ER -