Clearance of Clostridioides difficile colonization is associated with antibiotic-specific bacterial changes

Abstract

The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. difficile colonization. To elucidate the changes necessary to clear colonization, we compared differences in bacterial abundance between communities able and unable to clear C. difficile colonization. We treated mice with titrated doses of antibiotics prior to C. difficile challenge which resulted in no colonization, colonization and clearance, or persistent colonization. Previously, we observed that clindamycin-treated mice were susceptible to colonization but spontaneously cleared C. difficile. Therefore, we investigated whether other antibiotics would show the same result. We found reduced doses of cefoperazone and streptomycin permitted colonization and clearance of C. difficile. Mice that cleared colonization had antibiotic-specific community changes and predicted interactions with C. difficile. Clindamycin treatment led to a bloom in populations related to Enterobacteriaceae. Clearance of C. difficile was concurrent with the reduction of those blooming populations and the restoration of community members related to the Porphyromonadaceae and Bacteroides. Cefoperazone created a susceptible community characterized by a drastic reduction in the community diversity, interactions, and a sustained increase in abundance of many facultative anaerobes. Lastly, clearance in streptomycin-treated mice was associated with the recovery of multiple members of the Porphyromonadaceae, with little overlap in the specific Porphyromonadaceae observed in the clindamycin treatment. Further elucidation of how C. difficile colonization is cleared from different gut bacterial communities will improve C. difficile infection treatments.

Overview

project
|- README          # the top level description of content
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|- data            # raw and primary data, are not changed once created
|  |- references/  # reference files to be used in analysis
|  |- raw/         # raw data, will not be altered
|  |- mothur/      # mothur processed data
|  +- process/     # cleaned data, will not be altered once created;
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|- code/           # any programmatic code
|  |- bash         # bash scripts to process machine learning output
|  |- R            # R scripts to run machine learning model and process data
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|- submission      # files for manuscript
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|- config/        # modeling parameters for L2 logistic regression model
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|- scratch/        # temporary files that can be safely deleted or lost
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+- Makefile        # executable Makefile for this study