Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial

• Published in: EBioMedicine Vol. 38; pp. 265 - 272
• Main Authors: Wei, Shaodong, Mortensen, Martin Steen, Stokholm, Jakob, Brejnrod, Asker Daniel, Thorsen, Jonathan, Rasmussen, Morten Arendt, Trivedi, Urvish, Bisgaard, Hans, Sørensen, Søren Johannes
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2018; Elsevier
• Subjects: Antibiotics; Asthma; Azithromycin; Children; Gut microbiota; RCT; Research paper; Gut microbiota; RCT; Children; Antibiotics; Azithromycin; Asthma
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2018.11.035

Macrolides are commonly prescribed for respiratory infections and asthma-like episodes in children. While their clinical benefits have been proved, concerns regarding the side-effects of their therapeutic use have been raised. Here we assess the short- and long-term impacts of azithromycin on the gut microbiota of young children.
We performed a randomized, double-blind, placebo-controlled trial in a group of children aged 12–36 months, diagnosed with recurrent asthma-like symptoms from the COPSAC2010 cohort. Each acute asthma-like episode was randomized to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo. Azithromycin reduced episode duration by half, which was the primary end-point and reported previously. The assessment of gut microbiota after treatment was the secondary end-point and reported in this study. Fecal samples were collected 14 days after randomization (N = 59, short-term) and again at age 4 years (N = 49, long-term, of whom N = 18 were placebo treated) and investigated by 16S rRNA gene amplicon sequencing.
Short-term, azithromycin caused a 23% reduction in observed richness and 13% reduction in Shannon diversity. Microbiota composition was shifted primarily in the Actinobacteria phylum, especially a reduction of abundance in the genus Bifidobacterium. Long-term (13–39 months after treatment), we did not observe any differences between the azithromycin and placebo recipients in their gut microbiota composition.
Azithromycin treatment induced a perturbation in the gut microbiota 14 days after randomization but did not have long-lasting effects on the gut microbiota composition. However, it should be noted that our analyses included a limited number of fecal samples for the placebo treated group at age 4 years.
Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation, China Scholarship Council.