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EBioMedicine. 2018 Nov 23. pii: S2352-3964(18)30539-5. doi: 10.1016/j.ebiom.2018.11.035. [Epub ahead of print]

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

Author information

1
Department of Biology, Section of Microbiology, University of Copenhagen, Universitetsparken 15, bldg. 1, DK2100, Copenhagen, Denmark.
2
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Alle 34, 2820 Gentofte, Denmark.
3
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Alle 34, 2820 Gentofte, Denmark; Section of Chemometrics and Analytical Technologies, Department of Food Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
4
Department of Biology, Section of Microbiology, University of Copenhagen, Universitetsparken 15, bldg. 1, DK2100, Copenhagen, Denmark. Electronic address: SJS@bio.ku.dk.

Abstract

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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.

INTERPRETATION:

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. FUND: Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation, China Scholarship Council.

KEYWORDS:

Antibiotics; Asthma; Azithromycin; Children; Gut microbiota; RCT

PMID:
30478001
DOI:
10.1016/j.ebiom.2018.11.035
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