# Evaluating Effects of Antibiotics Across Preclinical Models of the Human Gastrointestinal Microbiota

## TL;DR

This study compares how antibiotics affect gut microbes in two lab models, showing that antibiotic effects vary widely and are influenced by the environment.

## Contribution

The study introduces a comprehensive comparison of antibiotic effects on gut microbiota using two preclinical models with different environmental contexts.

## Key findings

- Antibiotics affected a wide range of microbial taxa, including both Gram-positive and Gram-negative species.
- Vancomycin reduced the abundance of diverse taxa, including Bacteroidota species.
- Environmental context influenced antibiotic susceptibility, with some effects restricted to specific models.

## Abstract

While antibiotics play important roles in treating infections, disruption of the gastrointestinal microbiota during antibiotic treatment can lead to negative health consequences. However, for many antibiotics, the spectrum of activity has been determined for select isolates rather than for the range of microbes that populate the gastrointestinal tract. Here, we examined the response of communities of gastrointestinal microbes to antibiotics using two different model systems, human fecal minibioreactors and human microbiota‐associated mice. Communities established in minibioreactors using 12 different fecal donors were exposed to 12 different classes of antibiotics. Samples from three fecal donors were used to colonize germ‐free mice from three different genetic backgrounds; progeny mice were then exposed to 6 of 12 antibiotics tested in minibioreactors. Initial bacterial community diversity was dependent on both the fecal donor and model system. Antibiotics affected a wide range of taxa across the phylogenetic spectrum, with many taxa similarly affected across treatments with different classes of antibiotics. Vancomycin, typically administered to treat Gram‐positive bacterial infections, decreased the abundance of diverse taxa, including Gram‐negative Bacteroidota species. Effects on some taxa were restricted by model system, indicating the importance of environmental context on antibiotic susceptibility. Altogether, these results indicate the complex interrelationships between microbiota composition and environmental context on antibiotic susceptibility and demonstrate strengths and weaknesses of each preclinical model system for evaluating effects of new antibiotics and other compounds with potential to disrupt the microbiota.

We compared microbiota changes following antibiotic treatment in two preclinical models of the human GI microbiota, minibioreactor arrays (MBRAs) and human microbiota associated mice (HMAmice). MBRAs and HMAmice were colonized with feces from 12 or 3 healthy humans, respectively, before treatment with each of 12 or 6 antibiotics.