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

Clin Exp Allergy. 2013 Mar;43(3):353-64. doi: 10.1111/cea.12047.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Culture Media, Conditioned / pharmacology*
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism
  • Hypersensitivity / therapy
  • Immunologic Factors / pharmacology*
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation / therapy
  • Lacticaseibacillus rhamnosus / chemistry
  • Lacticaseibacillus rhamnosus / growth & development
  • Lacticaseibacillus rhamnosus / immunology*
  • Mice
  • Nod2 Signaling Adaptor Protein / metabolism
  • Probiotics*
  • Toll-Like Receptor 2 / metabolism


  • Culture Media, Conditioned
  • Immunologic Factors
  • Nod2 Signaling Adaptor Protein
  • Toll-Like Receptor 2