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Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled
Thuy Doan1,2, Ahmed M Arzika3, Kathryn J Ray1
1Francis I. Proctor Foundation, University of California San Francisco, San Francisco, California, United States of America.
Insights
Azithromycin significantly reduced gut microbiome diversity in children from an antibiotic-naive community in Niger. This study highlights the impact of antibiotic exposure on the gut microbiota of young children.
Area of Science:
- Microbiology
- Pediatrics
- Public Health
Background:
- Antibiotic exposure is known to alter the composition and diversity of the gut microbiome.
- The impact of antibiotics on the gut microbiome in antibiotic-naive populations, particularly in children, requires further investigation.
Purpose of the Study:
- To evaluate the effects of azithromycin on the gut microbiome diversity in children residing in an antibiotic-naive community in Niger.
- To assess changes in alpha (α), beta (β), and gamma (γ) diversity of the gut microbiome following azithromycin administration.
Main Methods:
- A randomized, placebo-controlled trial involving 80 children aged 1-60 months in Niger.
- Fecal samples were collected pre-treatment and 5 days post-treatment for 16S rRNA gene sequencing.
- Analysis included inverse Simpson's α-diversity, and Simpson's and Shannon's diversities for α, β, and γ diversity.
Main Results:
- Azithromycin treatment significantly reduced gut microbiome α-diversity compared to placebo (inverse Simpson's: 5.03 vs 6.91, P = .03; Shannon's: 10.60 vs 15.42, P = .004).
- Community-level (γ) diversity also decreased significantly in the azithromycin group (17.72 to 10.10, P = .00008).
- No significant reduction in β-diversity was observed (P = .26).
Conclusions:
- Single-dose oral azithromycin administration significantly decreases gut microbiome diversity in children from an antibiotic-naive community.
- These findings underscore the profound impact of azithromycin on the developing gut microbiome in vulnerable populations.
Background:
Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger.
Methods:
A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo. Fecal samples were collected immediately before treatment and 5 days after treatment for 16S rRNA gene sequencing. The prespecified outcome was α-diversity (inverse Simpson's α-diversity index), with secondary outcomes of β and γ Simpson's and Shannon's diversities.
Results:
At 5 days after treatment, 40 children aged 1-60 months were analyzed in the azithromycin-treated group and 40 children in the placebo-treated group. Diversity of the gut microbiome was significantly lower in the treated group (inverse Simpson's α-diversity, 5.03; 95% confidence interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P = .03). Similarly, the Shannon's α-diversity was lower in the treated group (10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P = .004). Simpson's community-level (γ) diversity decreased with azithromycin exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P = .00008), although β-diversity was not significantly reduced (2.56, 95% CI, 1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26).
Conclusions:
Oral administration of azithromycin definitively decreases the diversity of the gut microbiome of children in an antibiotic-naive community.
Clinical Trials Registration:
NCT02048007.