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

Clin Infect Dis. 2017 May 1;64(9):1147-1153. doi: 10.1093/cid/cix141.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Anti-Bacterial Agents / administration & dosage*
  • Azithromycin / administration & dosage*
  • Bacteria / classification
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Biodiversity
  • Child, Preschool
  • Cluster Analysis
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Infant
  • Male
  • Niger
  • Phylogeny
  • Placebos / administration & dosage
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA

Substances

  • Anti-Bacterial Agents
  • DNA, Ribosomal
  • Placebos
  • RNA, Ribosomal, 16S
  • Azithromycin

Associated data

  • ClinicalTrials.gov/NCT02048007