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 - 2018/12
Y1 - 2018/12
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
SN - 2352-3964
VL - 38
SP - 265
EP - 272
JO - EBioMedicine
JF - EBioMedicine
ER -