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

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Author: Harb, H. · Tol, E.A.F. van · Heine, H. · Braaksma, M. · Gross, G. · Overkamp, K. · Hennen, M. · Alrifai, M. · Conrad, M.L. · Renz, H. · Garn, H.
Type:article
Date:2013
Source:Clinical and Experimental Allergy, 3, 43, 353-364
Identifier: 471481
doi: doi:10.1111/cea.12047
Keywords: Biology · Asthma · LGG · Neonatal Animal Model · Prevention · Soluble Factors · Interleukin 10 · Probiotic Agent · Tumor Necrosis Factor Alpha · Allergic Airway Inflammation · Animal Cell · Animal Experiment · Article · Controlled Study · Cytokine Production · female · Helper Cell · Immunomodulation · In Vitro Study · In Vivo Study · Lactobacillus Rhamnosus · macrophage · Mouse · Newborn · Nonhuman · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · EELS - Earth, Environmental and Life Sciences

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. 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. © 2012 Blackwell Publishing Ltd.