TY - JOUR

T1 - Short- and long-term impacts of azithromycin treatment on the gut microbiota in children

T2 - a double-blind, randomized, placebo-controlled trial

AU - Wei, Shaodong

AU - Mortensen, Martin Steen

AU - Stokholm, Jakob

AU - Brejnrod, Asker Daniel

AU - Thorsen, Jonathan

AU - Rasmussen, Morten Arendt

AU - Trivedi, Urvish

AU - Bisgaard, Hans

AU - Sørensen, Søren Johannes

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Asthma

KW - Azithromycin

KW - Children

KW - Gut microbiota

KW - RCT

U2 - 10.1016/j.ebiom.2018.11.035

DO - 10.1016/j.ebiom.2018.11.035

M3 - Journal article

C2 - 30478001

AN - SCOPUS:85057003899

VL - 38

SP - 265

EP - 272

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -