title: Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute for Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
authors: H
authors: H
authors: Harb
authors: E A F
authors: EA
authors: van Tol
authors: H
authors: H
authors: Heine
authors: M
authors: M
authors: Braaksma
authors: G
authors: G
authors: Gross
authors: K
authors: K
authors: Overkamp
authors: M
authors: M
authors: Hennen
authors: M
authors: M
authors: Alrifai
authors: M L
authors: ML
authors: Conrad
authors: H
authors: H
authors: Renz
authors: H
authors: H
authors: Garn
mesh_terms: D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D052201:Lacticaseibacillus rhamnosus / Q000737:chemistry / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D019936:Probiotics; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D007155:Immunologic Factors; D053473:Nod2 Signaling Adaptor Protein; D051195:Toll-Like Receptor 2