Effect of antibiotic pre-treatment and pathogen challenge on the intestinal microbiota in mice.

Tadasu Iizumi,Martin J Blaser,Geraldine Vilmen,Guillermo I Perez Perez,Takako Taniguchi,Wataru Yamazaki,Zhan Gao,Alexander V Alekseyenko

doi:10.1186/s13099-016-0143-z

Tadasu Iizumi, Martin J Blaser + Show 6 more

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https://doi.org/10.1186/s13099-016-0143-z

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Abstract

BackgroundMore than 50 years after the discovery of antibiotics, bacterial infections have decreased substantially; however, antibiotics also may have negative effects such as increasing susceptibility to pathogens. An intact microbiome is an important line of defense against pathogens. We sought to determine the effect of orally administered antibiotics both on susceptibility to pathogens and on impact to the microbiome. We studied Campylobacter jejuni, one of the most common causes of human diarrhea, and Acinetobacter baumannii, which causes wound infections. We examined the effects of antibiotic treatment on the susceptibility of mice to those pathogens as well as their influence on the mouse gut microbiome.ResultsIn C57/BL6 mice models, we explored the effects of pathogen challenge, and antibiotic treatment on the intestinal microbiota. Mice were treated with either ciprofloxacin, penicillin, or water (control) for a 5-day period followed by a 5-day washout period prior to oral challenge with C. jejuni or A. baumannii to assess antibiotic effects on colonization susceptibility. Mice were successfully colonized with C. jejuni more than 118 days, but only transiently with A. baumannii. These challenges did not lead to any major effects on the composition of the gut microbiota. Although antibiotic pre-treatment did not modify pathogen colonization, it affected richness and community structure of the gut microbiome. However, the antibiotic dysbiosis was significantly reduced by pathogen challenge.ConclusionsWe conclude that despite gut microbiota disturbance, susceptibility to gut colonization by these pathogens was unchanged. The major gut microbiome disturbance produced by antibiotic treatment may be reduced by colonization with specific microbial taxa.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0143-z) contains supplementary material, which is available to authorized users.

Highlights

More than 50 years after the discovery of antibiotics, bacterial infections have decreased substantially; antibiotics may have negative effects such as increasing susceptibility to pathogens
We developed mouse models involving colonization with these human pathogens to address three questions germane to colonization resistance; (1) what is the extent to which pathogens such as C. jejuni or A. baumannii colonize the GI tract of mice; (2) how does such colonization affect the gut microbiota; and (3) does pre-treatment with antibiotics change microbiota compositions and affect susceptibility to colonization by these pathogens?
Quantifying bacteria in fecal DNA Assessing total DNA concentrations using Nanodrop and total bacterial log10 copy number/ng DNA by qPCR, we found that they were similar between the control animals and those treated with either after antibiotic or pathogen challenge (Additional file 1: Figure S3, panels a–j)

Summary

Introduction

More than 50 years after the discovery of antibiotics, bacterial infections have decreased substantially; antibiotics may have negative effects such as increasing susceptibility to pathogens. The clinical use of antibiotics has become massive in recent decades [7] Their use increases susceptibility to acquired pathogen, the underlying mechanisms are not well-understood [8]. Antibiotics change the composition of microbiota in the GI tract [9], affecting metabolic, hormonal, and immunological interactions between community and host, as well as intra-community interactions [10,11,12]. Or together, these effects may increase host susceptibility to infection by introduced pathogens

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