Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life

Authors

  • H. Harb,

    1. Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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    • Members of the German Center for Lung Research
  • E. A. F. van Tol,

    1. Mead Johnson Nutrition, Evansville, IN, USA
    2. Mead Johnson Nutrition, Nijmegen, The Netherlands
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  • H. Heine,

    1. Section of Immunoregulation, Research Center Borstel - Leibniz-Center for Biosciences and Medicine, Borstel, Germany
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    • Members of the German Center for Lung Research
  • M. Braaksma,

    1. Microbiology and Systems Biology, TNO, Zeist, The Netherlands
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  • G. Gross,

    1. Mead Johnson Nutrition, Evansville, IN, USA
    2. Mead Johnson Nutrition, Nijmegen, The Netherlands
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  • K. Overkamp,

    1. Microbiology and Systems Biology, TNO, Zeist, The Netherlands
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  • M. Hennen,

    1. Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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    • Members of the German Center for Lung Research
  • M. Alrifai,

    1. Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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  • M. L. Conrad,

    1. Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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    • Members of the German Center for Lung Research
  • H. Renz,

    1. Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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    • Members of the German Center for Lung Research
  • H. Garn

    Corresponding author
    • Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany
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    • Members of the German Center for Lung Research

Correspondence:

Dr. H. Garn, Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Biomedical Research Center, Philipps University of Marburg, Hans-Meerwein-Strasse 2, D - 35043 Marburg, Germany.

E-Mail: garn@staff.uni-marburg.de

Summary

Background

Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases.

Objective

The aim of this study was to investigate potential immunomodulatory and allergy-protective effects of processed Lactobacillus rhamnosus GG (LGG)-derived supernatants early in life in neonatal mice.

Methods

In vitro, RAW264.7 mouse macrophages were stimulated with viable LGG, LGG-derived supernatants, prepared from different growth phases, and different size fractions thereof, and pro- and anti-inflammatory cytokine production was analysed. Supernatant fractions were also treated with protease, DNAse or carbohydrate-digesting enzymes to define the nature of immunomodulatory components. In vivo, neonatal Balb/c mice were orally supplemented with differentially processed LGG supernatants. Starting at 4 weeks of age, a protocol of ovalbumin-induced acute allergic airway inflammation was applied and protective effects of processed LGG supernatants were assessed.

Results

Incubation of RAW264.7 cells with LGG-derived supernatants significantly increased TNFα and IL-10 production. These effects were not restricted to a particular molecular size fraction. Treatment with protease, but not with DNAse or carbohydrate-digesting enzymes, completely abolished the immunomodulatory activities. Incubation of TLR/NOD-transfected cells with LGG-derived supernatants revealed that recognition and signalling of bioactive components is mediated by TLR2 and NOD2. In vivo supplementation of newborn mice with processed LGG-derived supernatants resulted in pronounced protective effects on the allergic inflammatory response as reflected by reduced eosinophil numbers, modified T helper cell cytokine production, significantly less lung inflammation and reduced goblet cell numbers in comparison with sham-treated controls.

Conclusion

LGG-derived supernatants exert immunomodulatory activities, and neonatal administration of specifically processed supernatants may provide an alternative to viable probiotics in reducing allergic inflammatory responses.

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