Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial

Abstract

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.

Keywords: antibiotics.; azithromycin; children; gut microbiome; randomized controlled trial.

Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Figures

Figure 1.

Trial profile. Eighty of the eighty-seven healthy and eligible children aged 1–60 months from a single village were randomly assigned to either the placebo or azithromycin treated group, with samples from 80 children subjected to 16S rRNA gene analysis. No children were lost to follow-up.

Figure 2.

The gut microbial composition (A) of children and alpha-diversity indices (B, C) between treatment groups. A, The 10 most abundant genera were depicted for each sample between treatment groups at baseline and at 5 days after treatment. Distributions of the Simpson’s index (B) and the Shannon’s index (C) for the placebo-treated (gray lines) and azithromycin-treated (orange lines) groups.

Figure 3.

Differentially abundant genera between the placebo- and azithromycin-treated children. Genera are shaded gray when significantly more abundant in the placebo group (P < .001) and shaded orange when significantly more abundant in the azithromycin-treated group. Abbreviation: LDA, linear discriminant analysis.