The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice
Lei Xu,
Anil Surathu,
Isaac Raplee,
Ashok Chockalingam,
Sharron Stewart,
Lacey Walker,
Leonard Sacks,
Vikram Patel,
Zhihua Li,
Rodney Rouse
Affiliations
Lei Xu
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Anil Surathu
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Isaac Raplee
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Ashok Chockalingam
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Sharron Stewart
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Lacey Walker
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Leonard Sacks
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Medical Policy, White Oak Federal Research Center
Vikram Patel
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Zhihua Li
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
Rodney Rouse
U. S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, HFD-910, White Oak Federal Research Center
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.
