# Comparative Impacts of Oral Amoxicillin, Azithromycin, and Clindamycin on Gut Microbiota and Intestinal Homeostasis

## TL;DR

This study compares how three common antibiotics affect gut bacteria and intestinal health, finding that azithromycin causes the least harm while clindamycin causes lasting damage.

## Contribution

The study provides a comparative analysis of the gut microbiota and intestinal impacts of amoxicillin, azithromycin, and clindamycin in mice.

## Key findings

- Clindamycin caused severe and persistent gut dysbiosis and reduced SCFA production without recovery.
- Azithromycin had mild and reversible effects on gut microbiota and mucosal barrier function.
- Amoxicillin caused moderate disruption with partial recovery after two weeks.

## Abstract

Background: Amoxicillin, clindamycin and azithromycin are the most frequently prescribed antibiotics for odontogenic infections, but their comparative effects on gut microbiota and intestinal homeostasis remain insufficiently understood. Disruption of gut microbiota, short-chain fatty acid (SCFA) production, and mucosal barrier integrity may contribute to gastrointestinal symptoms. We aimed to compare the impacts of these antibiotics on gut microbiota, SCFA levels, and colonic goblet cells. Methods: C57BL/6N mice were treated with oral amoxicillin, clindamycin, or azithromycin at clinically relevant dosages. Cecal index, fecal water content, and diarrhea index were assessed during treatment and recovery. Gut microbiota composition and absolute bacterial abundance were determined using 16S rRNA amplicon absolute quantification sequencing. SCFAs in cecal contents were quantified by gas chromatography–mass spectrometry. Goblet cell abundance and Muc2 mRNA expression in colon tissues were evaluated using Alcian blue staining and RT-PCR. Results: Amoxicillin caused moderate increases in cecal index, reduced Ligilactobacillus abundance, increased Escherichia-Shigella, lowered SCFA levels, and decreased goblet cells and Muc2 expression, with partial recovery after two weeks. Clindamycin induced more severe dysbiosis, including sustained Proteobacteria expansion, persistent loss of beneficial taxa, 86–90% reduction in SCFA production, and lasting decreases in goblet cells and Muc2 expression without recovery during the observation period. Azithromycin caused mild and reversible changes across all parameters. Conclusions: Among the three antibiotics, azithromycin had the least detrimental effects on gut microbiota, SCFA production, and mucosal barrier function, whereas clindamycin caused profound and persistent intestinal disruption. These findings provide comparative evidence to inform antibiotic selection in clinical practices.