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Antibiotics promote inflammation through the translocation of native commensal colonic bacteria
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Antibiotics promote inflammation through the translocation of native commensal colonic bacteria
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Journal Article
Antibiotics promote inflammation through the translocation of native commensal colonic bacteria
2016
Overview
ObjectiveAntibiotic use is associated with an increased risk of developing multiple inflammatory disorders, which in turn are linked to alterations in the intestinal microbiota. How these alterations in the intestinal microbiota translate into an increased risk for inflammatory responses is largely unknown. Here we investigated whether and how antibiotics promote inflammation via the translocation of live native gut commensal bacteria.DesignOral antibiotics were given to wildtype and induced mutant mouse strains, and the effects on bacterial translocation, inflammatory responses and the susceptibility to colitis were evaluated. The sources of the bacteria and the pathways required for bacterial translocation were evaluated using induced mutant mouse strains, 16s rRNA sequencing to characterise the microbial communities, and in vivo and ex vivo imaging techniques.ResultsOral antibiotics induced the translocation of live native commensal bacteria across the colonic epithelium, promoting inflammatory responses, and predisposing to increased disease in response to coincident injury. Bacterial translocation resulted from decreased microbial signals delivered to colonic goblet cells (GCs), was associated with the formation of colonic GC-associated antigen passages, was abolished when GCs were depleted and required CX3CR1+ dendritic cells. Bacterial translocation occurred following a single dose of most antibiotics tested, and the predisposition for increased inflammation was only associated with antibiotics inducing bacterial translocation.ConclusionsThese findings reveal an unexpected outcome of antibiotic therapy and suggest that bacterial translocation as a result of alterations in the intestinal microflora may provide a link between increasing antibiotic use and the increased incidence of inflammatory disorders.
Publisher
BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
Subject
/ Anti-Bacterial Agents - pharmacology
/ Bacteria
/ Bacterial Translocation - drug effects
/ Bacterial Translocation - immunology
/ Colitis
/ Colon
/ Enterococcus faecalis - isolation & purification
/ Escherichia coli - isolation & purification
/ Intestine, Small - microbiology
/ Mice
/ Mutants
/ Myeloid Differentiation Factor 88
/ Principal components analysis
/ Receptors, Chemokine - analysis
/ rRNA 16S
/ Studies
