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Updated: Jul 5, 2025
Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment
Published on: November 17, 2018
Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A
Thuy Doan1,2, Zijun Liu2, Ali Sié3
1Francis I. Proctor Foundation, University of California, San Francisco, California.
Insights
A single dose of azithromycin in young children temporarily reduced gut microbiome diversity and increased macrolide resistance genes. These effects were transient, resolving within six months, with no observed co-resistance to other antibiotics.
Area of Science:
- Microbiome research
- Antibiotic resistance
- Pediatric infectious diseases
Background:
- Mass antibiotic distribution can impact child gut microbiomes.
- Understanding the effects of azithromycin on the pediatric gut microbiome and resistome is crucial.
Purpose of the Study:
- To evaluate changes in the gut microbiome and resistome after a single oral dose of azithromycin in young children.
- To assess the transient or persistent effects of azithromycin on gut bacterial diversity and antimicrobial resistance determinants.
Main Methods:
- Individually randomized, placebo-controlled trial with 450 children aged 8 days to 59 months in Burkina Faso.
- Rectal samples collected at baseline, 2 weeks, and 6 months post-randomization.
- DNA deep sequencing to analyze gut microbiome diversity and antimicrobial resistance genes.
Main Results:
- Azithromycin significantly decreased gut bacterial diversity (Shannon and inverse Simpson indices) at 2 weeks post-treatment compared to placebo.
- A 243-fold increase in macrolide resistance genetic determinants was observed at 2 weeks.
- Microbiome alterations and increased macrolide resistance were not detected at the 6-month follow-up.
- No significant changes in resistance determinants for other antibiotic classes were observed.
Conclusions:
- A single dose of azithromycin transiently disrupts the gut microbiome and increases macrolide resistance in young children.
- The observed disruptions appear to be temporary, with recovery by 6 months.
- Individual-level azithromycin treatment is unlikely to drive co-resistance to other antibiotic classes.
Abstract:
Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.
