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Updated: Mar 3, 2026
Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment
Published on: November 17, 2018
Models of antimicrobial pressure on intestinal bacteria of the treated host populations
V V Volkova1, C L Cazer2, Y T Gröhn2
1Department of Diagnostic Medicine/Pathobiology, Institute of Computational Comparative Medicine, College of Veterinary Medicine, Kansas State University, Mosier Hall, KS 66506, USA.
Abstract:
Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.
Insights
Understanding antimicrobial drug concentrations in animal intestines is crucial for predicting their impact on gut bacteria. This study models key factors influencing drug levels, aiding in managing selective pressures from treatments.
Area of Science:
- Pharmacokinetics and Environmental Microbiology
- Veterinary Pharmacology and Toxicology
Background:
- Antimicrobial drugs are vital for treating bacterial infections in humans and animals.
- Enteric bacteria in hosts can be exposed to antimicrobials or their active metabolites in the intestine.
- Predicting antimicrobial concentrations in the host intestine is essential for understanding their effects on commensal bacteria.
Purpose of the Study:
- To identify and model key processes and variables influencing antimicrobial concentrations within the host intestine.
- To develop a framework for projecting antimicrobial levels and their selective pressures on enteric bacteria.
- To illustrate the modeling framework with examples of chlortetracycline and ceftiofur treatments in cattle.
Main Methods:
- Compilation of variables affecting antimicrobial concentrations: biliary excretion, other excretion routes, absorption/re-absorption rates and segments, degradation rates and segments, digesta passage time, sorption dynamics, and luminal volume.
- Consideration of factors influencing antimicrobial activity, such as intestinal aeration and chemical conditions.
- Development of model forms accounting for inter-individual variation in relevant variables.
- Illustrative simulations using oral chlortetracycline and injectable ceftiofur for bovine respiratory disease in beef steers, considering two diet compositions.
Main Results:
- The study outlines a comprehensive set of variables critical for modeling intestinal antimicrobial concentrations.
- The proposed framework allows for projections of antimicrobial concentrations and potential selective pressures on enteric bacteria.
- Illustrative examples demonstrate the application of the model and highlight data gaps regarding diet influences on antimicrobial fate and effects.
Conclusions:
- Accurate projection of intestinal antimicrobial concentrations requires accounting for numerous drug- and host-specific variables.
- The developed modeling framework provides a basis for assessing antimicrobial selective pressures on the host's enteric microbiome.
- Further empirical data is needed to refine models and understand the complex interactions between antimicrobials, host factors, and the intestinal environment.
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01:28Antimicrobial Effectiveness
01:28Biological Methods for Microbial Control
01:30Development of Antibiotic Resistance
01:31Defense Against Bacterial Pathogens
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