Unveiling the Differential Impacts of Antibiotics on Gut Microbiota and Implications for Antimicrobial Stewardship

Mouse data rank oral antibiotics by microbiome disruption—clindamycin worst, amoxicillin intermediate, azithromycin least—highlighting differential C. difficile risk and mucosal injury.

The mouse-model study demonstrates that oral antibiotics differ markedly in microbiota disruption: amoxicillin produced moderate dysbiosis with partial recovery, azithromycin produced mild and reversible shifts, and clindamycin produced severe, persistent loss of community structure.

In a C57BL/6N mouse model, investigators administered clinically relevant oral doses and followed outcomes during treatment and across a two‑week recovery window. Primary endpoints included absolute microbiota composition by 16S quantification, cecal short‑chain fatty acids measured by GC–MS, and colonic Muc2 expression plus goblet cell abundance. Sample‑level measures (cecal index, fecal water content) and histologic markers linked compositional shifts to barrier biology; these endpoints were chosen to directly inform infection risk and mucosal function.

Amoxicillin induced a moderate compositional shift with depletion of select beneficial taxa and an increase in facultative Enterobacterales, followed by partial normalization within the two‑week recovery window. By contrast, azithromycin produced smaller, short‑lived changes that largely returned toward baseline during the observation period, indicating more rapid recovery. Overall, azithromycin showed the least microbiome disturbance while amoxicillin carried an intermediate disruption profile.

The study found that clindamycin caused the most profound and persistent dysbiosis, characterized by near‑complete reductions in beneficial short‑chain fatty acids (on the order of an ~86–90% decrease), marked Proteobacteria expansion where present, and substantial decreases in Muc2 expression with goblet cell depletion that failed to recover over two weeks. These biologic effects—severe SCFA loss and impaired mucosal markers—map directly to increased vulnerability to C. difficile colonization and weakened mucosal defense.