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G Protein-Coupled Receptor 109A and Host Microbiota Modulate Intestinal Epithelial Integrity During Sepsis
- Source :
- Frontiers in Immunology, Vol 9 (2018)
- Publication Year :
- 2018
- Publisher :
- Frontiers Media SA, 2018.
-
Abstract
- The intestinal epithelial barrier is important to mucosal immunity, although how it is maintained after damage is unclear. Here, we show that G protein-coupled receptor 109A (GPR109A) supports barrier integrity and decreases mortality in a mouse cecum ligation and puncture (CLP) sepsis model. Data from 16S RNA sequencing showed that the intestinal microbiota of WT and Gpr109a−/− mice clustered differently and their compositions were disrupted after CLP surgery. GPR109A-deficient mice showed increased mortality, intestinal permeability, altered inflammation, and lower tight junction gene expression. After eliminating the intestinal flora with antibiotics, all experimental mice died within 48 h of CLP surgery. This demonstrates the critical role of the gut microbiota in CLP-induced sepsis. Importantly, mortality and other pathologies in the model were decreased after Gpr109a−/− mice received WT gut microbiota. These findings indicate that GPR109A regulates the gut microbiota, contributing to intestinal epithelial barrier integrity and decreased mortality in CLP-induced sepsis.
- Subjects :
- lcsh:Immunologic diseases. Allergy
0301 basic medicine
medicine.drug_class
Immunology
Antibiotics
Inflammation
Gut flora
digestive system
Permeability
Receptors, G-Protein-Coupled
Tight Junctions
Microbiology
sepsis
Sepsis
Mice
03 medical and health sciences
RNA, Ribosomal, 16S
Gene expression
medicine
Animals
Humans
Immunology and Allergy
Intestinal Mucosa
Receptor
Cecum
Mice, Knockout
Intestinal permeability
gut microbiota
biology
Tight junction
biology.organism_classification
medicine.disease
GPR109A
Gastrointestinal Microbiome
Mice, Inbred C57BL
Disease Models, Animal
stomatognathic diseases
030104 developmental biology
intestinal epithelial barrier
Host-Pathogen Interactions
Female
CLP
medicine.symptom
lcsh:RC581-607
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....10993fbd1e76f02b14bd1e48a29e7c9e