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Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
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Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
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Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

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Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy
Journal Article

Antibiotics induced intestinal tight junction barrier dysfunction is associated with microbiota dysbiosis, activated NLRP3 inflammasome and autophagy

2019
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Overview
Tight junction barrier is critical to intestinal homeostasis. Applying antibiotics to treat infections is common in clinical practice, which may affect intestinal microbiota. Intestinal microbiota dysbiosis is involved in the occurrence of some gastrointestinal diseases. Therefore, this study was aimed to investigate the influence of antibiotics on intestinal tight junction barrier and the possible underlying mechanisms. Healthy adult female C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail for 14 days. 16S rDNA Illumina sequencing and headspace gas chromatography-mass spectrometry (HS-GC/MS) were respectively used to analyze microbial community and to detect short-chain fatty acids (SCFAs) contents. In vivo intestinal paracellular permeability to fluorescein isothiocyanate-dextran (FITC-dextran) was measured. Protein expression was determined by immunoblotting. Immunofluoresence was applied to observe the distributions of ZO-1, LC3B and ASC. Antibiotics remarkably altered intestinal microbiota composition in healthy mice, accompanying reduced SCFAs' concentrations. In addition, the intestinal tight junction barrier was disrupted by antibiotic treatment, as evidenced by increased intestinal paracellular permeability to FITC-dextran, decreased tight junction protein expressions, and disrupted ZO-1 morphology. Furthermore, NLRP3 inflammasome and autophagy were activated by antibiotic treatment. In conclusion, intestinal epithelial tight junction barrier dysfunction induced by antibiotics is associated with intestinal microbiota dysbiosis, activated NLRP3 inflammasome and autophagy in mice.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject

Analysis

/ Animals

/ Anti-Bacterial Agents - adverse effects

/ Anti-Bacterial Agents - pharmacology

/ Antibiotics

/ Autophagy

/ Autophagy (Cytology)

/ Autophagy - drug effects

/ Bacterial infections

/ Binding sites

/ Biology and Life Sciences

/ Burns

/ Cell death

/ Chromatography

/ Complications and side effects

/ Development and progression

/ Dextran

/ Dextrans

/ Dextrans - chemistry

/ Disease Models, Animal

/ DNA sequencing

/ DNA, Ribosomal - genetics

/ Dysbacteriosis

/ Dysbiosis

/ Dysbiosis - chemically induced

/ Dysbiosis - microbiology

/ Dysbiosis - pathology

/ Fatty acids

/ Fatty Acids, Volatile - metabolism

/ Fluorescein

/ Fluorescein isothiocyanate

/ Fluorescein-5-isothiocyanate - analogs & derivatives

/ Fluorescein-5-isothiocyanate - chemistry

/ Gas chromatography

/ Gastrointestinal diseases

/ Gene Expression Regulation - drug effects

/ Headspace

/ Health aspects

/ Homeostasis

/ Hospitals

/ House mouse

/ Humans

/ Immune system

/ Immunoblotting

/ Infection

/ Inflammasomes

/ Inflammasomes - drug effects

/ Inflammasomes - metabolism

/ Inflammatory bowel disease

/ Intestinal microflora

/ Intestine

/ Intestines - drug effects

/ Intestines - microbiology

/ Intestines - pathology

/ Ischemia

/ Laboratories

/ Mass spectrometry

/ Mass spectroscopy

/ Medical research

/ Medicine and Health Sciences

/ Mice

/ Microbiota

/ Microbiota (Symbiotic organisms)

/ Microbiota - drug effects

/ Microorganisms

/ Morphology

/ NLR Family, Pyrin Domain-Containing 3 Protein - genetics

/ Pathogens

/ Permeability

/ Phagocytosis

/ Physical Sciences

/ Polysaccharides

/ Proteins

/ rRNA 16S

/ Spectroscopy

/ Tight Junctions - drug effects

/ Tight Junctions - microbiology

/ Tight Junctions - pathology

/ Trauma

/ Zonula occludens-1 protein