Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model

Publication date: Available online 24 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Anna Strzępa, Monika Majewska-Szczepanik, Francis M. Lobo, Li Wen, Marian Szczepanik
BackgroundMedical advances in the field of infection therapy has led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases including autoimmunity and allergy.ObjectiveWe sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice.MethodsNatural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with TNP-Cl followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification.ResultsOral treatment with enrofloxacin suppresses CS and production of anti-TNP IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCRαβ⁺CD4⁺CD25⁺FoxP3⁺ Treg, CD19⁺B220⁺CD5⁺IL-10⁺, IL-10⁺ Tr1, and IL-10⁺TCRγδ⁺ cells. Treatment with the antibiotic induces dysbiosis characterised by increased proportion of Clostridium coccoides (cluster XIVa), Clostridium coccoides – E. rectale (cluster XIVab), Bacteroidetes and Bifidobacterium spp., but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals.ConclusionOral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.

Teaser

Antibiotic-induced dysbiosis, characterized by increased levels of Bacteroidetes, Bifidobacterium spp., Clostridium cluster XIVa and XIVab, but decreased proportions of segmented filamentous bacteria, effectively inhibits contact sensitivity by inducing a variety of regulatory cells.


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