The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice

Abstract

Background: Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. Methods: This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance. Results: There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group). Conclusions: Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.

Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment

“…For other pathogens studied, for example Campylobacter coli in the Ciprofloxacin cohort, we found that while the relative abundance is not increased, the numbers of ARGs are, suggesting more ARG-enriched subpopulations were selected by the treatment. Interestingly, our previous study suggested that ARGs enriched in cohorts treated by one class of antibiotics are often resistant to other classes of antibiotics [14]. We also observed that some opportunistic pathogens have more ARG-associated reads in control compared to antibody-treated groups (Fig.…”

“…All mice, except two of the three control mice, were inoculated with CFT073 uropathogenic E.coli (ATCC, Manassas, VA) to create the UTI model. Our previous study showed no discernable difference in the gut microbiome of naïve and urinary tract infection model mice [14]. Treatment groups include antibiotics Ampicillin, Ciprofloxacin, and Fosfomycin.…”

“…Genomic DNA extraction and sequencing was completed as previously described [14]. Briefly, collected fecal samples had DNA extracted using QIAamp DNA stool mini kit (Qiagen, Germantown, MD) with slight modifications to the protocol.…”

“…Recently we applied a traditional read-mapping based method to the metagenome analysis of antibiotic treated mice and revealed a decrease of gut microbiota diversity and enrichment of antibiotic resistance genes (ARGs) in the gut [14]. However, as with many other studies, the read-mapping method left a large portion of the reads uncharacterized.…”

Metagenomic analysis revealed a wide distribution of antibiotic resistance genes and biosynthesis of antibiotics in the gut of giant pandas

“…Interestingly, acrB, an efflux membrane transporter that conferred resistance to several antibiotics classes, negatively associated with diet and was not among the top-ten ARGs of juveniles. Efflux pumps are a part of bacteria’s intrinsic resistance mechanism and decrease different antibiotic concentrations within the cell wall [ 55 ]. Since efflux pumps can be transferred horizontally [ 56 ], the presence of acrB in adults and geriatrics could be involved in horizontal gene transfer events [ 57 ].…”