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Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment
Zuzana Zakostelska, Miloslav Kverka, Klara Klimesova, Pavel Rossmann, Jakub Mrazek, Jan Kopecny, Michaela Hornova, Dagmar Srutkova, Tomas Hudcovic, Jakub Ridl, Helena Tlaskalova-Hogenova
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
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NS10340
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- MeSH
- Macrophage Activation drug effects MeSH
- Acute Disease MeSH
- Administration, Oral MeSH
- Down-Regulation drug effects MeSH
- Phosphoproteins metabolism MeSH
- Immunity drug effects MeSH
- Colitis microbiology pathology physiopathology prevention & control MeSH
- Lacticaseibacillus casei metabolism MeSH
- Humans MeSH
- Lipopolysaccharides pharmacology MeSH
- Membrane Proteins metabolism MeSH
- Metagenome drug effects MeSH
- Mice, Inbred BALB C MeSH
- Mice, SCID MeSH
- Mice MeSH
- NF-kappa B metabolism MeSH
- Permeability drug effects MeSH
- Lymphocyte Count MeSH
- Probiotics administration & dosage pharmacology MeSH
- T-Lymphocytes, Regulatory cytology drug effects MeSH
- Intestinal Mucosa drug effects immunology microbiology MeSH
- Tumor Necrosis Factor-alpha biosynthesis MeSH
- Digestive System drug effects microbiology physiopathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Probiotic bacteria can be used for the prevention and treatment of human inflammatory diseases including inflammatory bowel diseases (IBD). However, the nature of active components and exact mechanisms of this beneficial effects have not been fully elucidated. Our aim was to investigate if lysate of probiotic bacterium L. casei DN-114 001 (Lc) could decrease the severity of intestinal inflammation in a murine model of IBD. METHODOLOGY/PRINCIPAL FINDINGS: The preventive effect of oral administration of Lc significantly reduces the severity of acute dextran sulfate sodium (DSS) colitis in BALB/c but not in SCID mice. In order to analyze how this beneficial effect interferes with well-known phases of intestinal inflammation pathogenesis in vivo and in vitro, we evaluated intestinal permeability using the FITC-labeled dextran method and analysed tight junction proteins expression by immunofluorescence and PCR. We also measured CD4(+)FoxP3(+) regulatory T cells proportion by FACS analysis, microbiota composition by pyrosequencing, and local cytokine production by ELISA. Lc leads to a significant protection against increased intestinal permeability and barrier dysfunction shown by preserved ZO-1 expression. We found that the Lc treatment increases the numbers of CD4(+)FoxP3(+) regulatory T cells in mesenteric lymph nodes (MLN), decreases production of pro-inflammatory cytokines TNF-α and IFN-γ, and anti-inflammatory IL-10 in Peyer's patches and large intestine, and changes the gut microbiota composition. Moreover, Lc treatment prevents lipopolysaccharide-induced TNF-α expression in RAW 264.7 cell line by down-regulating the NF-κB signaling pathway. CONCLUSION/SIGNIFICANCE: Our study provided evidence that even non-living probiotic bacteria can prevent the development of severe forms of intestinal inflammation by strengthening the integrity of intestinal barrier and modulation of gut microenvironment.
Institute of Microbiology Academy of Sciences of the Czech Republic Novy Hradek Czech Republic
Institute of Microbiology Academy of Sciences of the Czech Republic Prague Czech Republic
Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague Czech Republic
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