Long-Term Antibiotic-Driven Gut Microbiota Disruption Promotes Toxigenic Clostridioides difficile Proliferation: A...

This four-year longitudinal study of a single critically ill patient leverages deep temporal profiling to unravel the dynamic interplay between antibiotic pressure, gut microbiota, and Clostridioides difficile (C. difficile) colonization, providing temporal insights unattainable through cross-sectional designs.

We performed a retrospective analysis of one critically ill patient (2015-2019). Sixty-four fecal samples were subjected to toxigenic C. difficile culture and metagenomic sequencing. To isolate short-term effects, we implemented a 7-day retrospective window, categorizing each sample based on antibiotic exposure in the preceding week: no antibiotics, monotherapy, or polypharmacy.

Antibiotic exposure significantly reduced microbial diversity and promoted dysbiosis. Crucially, we identified a transitional C. difficile colonization state (Tcd±) that potentially determines progression to toxigenic (Tcd+) or non-toxigenic (Tcd-) outcomes. Analysis using the 7-day window revealed that intensive antibiotic pressure was strongly associated with successional progression towards toxigenic dominance. Conversely, brief antibiotic-free intervals were linked to partial restoration of microbial network complexity and a competitive landscape favoring non-toxigenic strains.

This deep temporal profiling of a single case provides novel, hypothesis-generating insights. The identification of a transitional colonization state and the association between short-term antibiotic pressure and colonization outcomes define critical dynamics for future validation. These findings highlight the potential of longitudinal data to inform precise antibiotic stewardship strategies in high-risk, critically ill populations.