Abstract
The aim of this study was to establish continuous therapeutic-dose ampicillin (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with a view to using this to assess its impact on gut microbiota, intestinal metabolites and host immune responses. Mice were exposed to ampicillin for 14 days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota and gut permeability. The cecal index was increased in the CTDA group, and the gut permeability indicated by fluorescent dextran, endotoxin and D-Lactate in the serum was significantly increased after antibiotic use. The tight-junction proteins ZO-1 and occludin in the colon were reduced to half the control level in CTDA. We found that alpha-diversity was significantly decreased in mice receiving CTDA, and microbial community structure was altered compared with the control. Key taxa were identified as CTDA-specific, and the relative abundance of Enterococcus and Klebsiella was particularly enriched while Lachnospiraceae, Coprobacillus and Dorea were depleted after antibiotic treatment. In particular, a significant increase in succinate and a reduction in butyrate was detected in CTDA mice, and the triggering of NF-κB enhancement reflected that the host immune response was influenced by ampicillin use. The observed perturbation of the microbiota was accompanied by modulation of inflammatory state; this included increase in interferon-γ and RegIIIγ, and a decrease in secretory IgA in the colon mucosa. This study allowed us to identify the key taxa associated with an ampicillin-induced state of dysbiosis in mice and to characterize the microbial communities via molecular profiling. Thus, this work describes the bacterial ecology of antibiotic exposure model in combination with host physiological characteristics at a detailed level of microbial taxa.
Highlights
Since their discovery in the early twentieth century, antibiotics have been used widely
We examined 16S rRNA gene sequences to determine the effects of ampicillin on the diversity of the colonic microbiota
These results indicate that continuous therapeutic-dose ampicillin (CTDA) treatment selected for a distinctive microbial community structure, and the diversity and structure of the colonic microbiota among treatment groups and the Control group were more distinct following ampicillin administration over an increased period of time
Summary
Since their discovery in the early twentieth century, antibiotics have been used widely. Antibiotics are often used inappropriately; for example, they may be prescribed for short periods to treat flu or acute infections, or added to animal feed as growth promoters (Vigre et al, 2008; Zhou et al, 2013). This overuse and misuse of antibiotics is a worldwide problem, including in China, and there are growing concerns that antibiotic exposure may lead to short-term and/or long-term negative health consequences (Hvistendahl, 2012; Wang et al, 2015). Antibiotic-induced alteration of the gut microbiota could lead to metabolic disorders, such as inflammatory bowel disease, diabetes and obesity (Cho et al, 2012; Boursi et al, 2015; Becattini et al, 2016)
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