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Bifidobacterium longum subsp. infantis in experimental necrotizing enterocolitis: alterations in inflammation, innate immune response, and the microbiota

  • 2014-07-07
  • Pediatric Research 76(4)
    • M. Underwood
    • J. Arriola
    • Colin W. Gerber
    • Ashwini Kaveti
    • K. Kalanetra
    • Anchasa Kananurak
    • C. Bevins
    • D. Mills
    • B. Dvořák

Abstract

Background: Probiotics decrease the risk of necrotizing enterocolitis (NEC). We sought to determine the impact of Bifidobacterium longum subsp. infantis (B. infantis) in the established rat model of NEC.

Methods: Rat pups delivered 1 d prior to term gestation were assigned to one of three groups: dam fed (DF), formula fed (FF), or fed with formula supplemented with 5 × 10(6) CFU B. infantis per day (FF+Binf). Experimental pups were exposed to hypoxia and cold stress. Ileal tissue was examined for pathology and expression of inflammatory mediators, antimicrobial peptides, and goblet-cell products. Ceca were assessed for bacterial composition by analysis of the 16S rRNA sequence.

Results: Administration of B. infantis significantly reduced the incidence of NEC, decreased expression of Il6, Cxcl1, Tnfa, Il23, and iNOS, and decreased expression of the antimicrobial peptides Reg3b and Reg3g. There was significant microbial heterogeneity both within groups and between experiments. The cecal microbiota was not significantly different between the FF and FF+Binf groups. Bifidobacteria were not detected in the cecum in significant numbers.

Conclusion: In the rat model, the inflammation associated with NEC was attenuated by administration of probiotic B. infantis. Dysbiosis was highly variable, precluding determination of the precise role of the microbiota in experimental NEC.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Bifidobacterium infantisReduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantisReduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantisReduced Occurrence of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis BI02No Significant Change in Cecal Microbiota CompositionNeutral
Small
Bifidobacterium infantis BI02Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis BI02Reduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantis BI02Reduced Risk of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis HA-116Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis HA-116Reduced Proinflammatory Cytokine ExpressionBeneficial
Moderate
Bifidobacterium infantis HA-116Reduced Risk of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis M-63Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis M-63Reduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantis M-63Reduced Occurrence of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis MAK22B04IAltered Innate Immune ResponseBeneficial
Large
Bifidobacterium infantis MAK22B04IReduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis MAK22B04IReduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantis MAK22B04IReduced Occurrence of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis SD-6720Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis SD-6720Reduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantis SD-6720Reduced Risk of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium infantis VPro 53Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium infantis VPro 53Reduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium infantis VPro 53Reduced NEC IncidenceBeneficial
Large
Bifidobacterium longum subsp. infantisReduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium longum subsp. infantisReduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium longum subsp. infantisReduced Occurrence of Necrotizing EnterocolitisBeneficial
Large
Bifidobacterium longum subsp. infantis M-63Reduced Antimicrobial Peptide ExpressionBeneficial
Moderate
Bifidobacterium longum subsp. infantis M-63Reduced Inflammatory Mediators ExpressionBeneficial
Large
Bifidobacterium longum subsp. infantis M-63Reduced Occurrence of Necrotizing EnterocolitisBeneficial
Large
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