Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization.
Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans.
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Hana
H
Kozakova
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Martin
M
Schwarzer
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Ludmila
L
Tuckova
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Dagmar
D
Srutkova
Department of Pathology, the Children's Memorial Health Institute, Warsaw, Poland.
Elzbieta
E
Czarnowska
Department of Pathology, the Children's Memorial Health Institute, Warsaw, Poland.
Ilona
I
Rosiak
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Tomas
T
Hudcovic
Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Irma
I
Schabussova
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Petra
P
Hermanova
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Zuzana
Z
Zakostelska
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Tamara
T
Aleksandrzak-Piekarczyk
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Anna
A
Koryszewska-Baginska
Laboratory of Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
Helena
H
Tlaskalova-Hogenova
Department of Pathology, the Children's Memorial Health Institute, Warsaw, Poland.
Bozena
B
Cukrowska
D000818:Animals; D052179:Antigens, Plant / Q000633:toxicity; D005856:Germ-Free Life / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D007780:Lacticaseibacillus casei / Q000276:immunology*; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology
D052179:Antigens, Plant; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C061312:Bet v 1 allergen, Betula