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Updated: Jun 12, 2026

In Vitro Apical-Out Enteroid Model of Necrotizing Enterocolitis
Published on: June 8, 2022
Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis
Ludmila Khailova1, Katerina Dvorak, Kelly M Arganbright
1Department of Pediatrics, University of Arizona, Tucson, Arizona 85724-5073, USA.
Insights
Bifidobacterium bifidum significantly reduced necrotizing enterocolitis (NEC) incidence in premature rats. This probiotic improved intestinal integrity and regulated inflammatory responses, offering a promising preventative strategy for NEC.
Area of Science:
- Neonatal research
- Gastroenterology
- Microbiology
Background:
- Necrotizing enterocolitis (NEC) is a severe condition affecting premature infants.
- Probiotics are explored for NEC prevention, but mechanisms remain unclear.
Purpose of the Study:
- To investigate Bifidobacterium bifidum's protective effects against NEC in a rat model.
- To assess B. bifidum's impact on cytokine regulation and intestinal barrier function.
Main Methods:
- A rat model of NEC was established using premature neonates exposed to asphyxia and cold stress.
- Rats were divided into dam-fed, NEC, and B. bifidum-supplemented groups.
- Intestinal injury, mucin, Tff3, cytokines, and junction proteins were analyzed.
Main Results:
- B. bifidum reduced NEC incidence from 57% to 17%.
- Probiotic treatment normalized elevated IL-6, mucin-3, and Tff3 levels.
- B. bifidum improved tight junction and adherens junction protein expression and localization.
Conclusions:
- Bifidobacterium bifidum administration protects against NEC in neonatal rats.
- Protection is linked to reduced ileal inflammation and enhanced intestinal integrity.
- B. bifidum modulates mucus layer components and improves gut barrier function.
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.
