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Longitudinal Gut Microbiome Changes Associated with Transitions from C. difficile Negative to C. difficile Positive
L Silvia Munoz-Price1, Samantha N Atkinson2, Vy Lam3
1Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Microorganisms
|October 29, 2025
Summary
The transition to Clostridioides difficile colonization alters gut microbial communities. This study reveals significant microbiome changes, including increased Pseudomonadota and Enterobacteriaceae, during C. difficile acquisition.
Area of Science:
- Microbiology
- Gut Microbiome Research
- Infectious Disease Dynamics
Background:
- Clostridioides difficile (C. difficile) infection is a major healthcare concern, primarily transmitted via the fecal-oral route.
- Understanding microbiome shifts during C. difficile colonization is crucial for developing targeted interventions.
- Current data on microbiome changes during the transition from non-colonized to C. difficile colonized states are limited.
Purpose of the Study:
- To characterize the dynamic changes in the gut microbiome composition during the transition to C. difficile colonization.
- To identify specific microbial taxa alterations associated with C. difficile acquisition and persistent carriage.
- To investigate the role of microbiome dysbiosis in C. difficile colonization and disease.
Main Methods:
- Retrospective cohort study analyzing 16S rRNA gene sequencing data from 481 fecal samples of 107 patients.
- Patients categorized into Negative-to-Positive, Negative Control, and Positive Control groups based on C. difficile status over time.
- Statistical models (linear mixed effects, zero-inflated negative binomial/Poisson mixed effects) used to analyze changes in alpha-diversity and taxon counts.
Main Results:
- Significant differences in microbiome composition were observed between last negative and first positive samples in the Negative-to-Positive group (ANOSIM p = 0.022).
- Phylum Pseudomonadota and family Enterobacteriaceae significantly increased in Negative-to-Positive patients upon C. difficile acquisition (p = 0.0075 and p = 0.0094, respectively).
- Actinomycetota decreased in the Positive Control group, while Bacillota decreased in both Negative-to-Positive and Positive Control groups over time.
Conclusions:
- The transition from C. difficile negative to positive status is marked by significant alterations in gut microbial communities.
- Specific bacterial phyla and families show dynamic changes correlating with C. difficile colonization.
- These microbiome shifts contribute to gut dysbiosis, impacting C. difficile colonization and persistence.
