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

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 azithromyc...

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Autores principales: Wei, Shaodong, Mortensen, Martin Steen, Stokholm, Jakob, Brejnrod, Asker Daniel, Thorsen, Jonathan, Rasmussen, Morten Arendt, Trivedi, Urvish, Bisgaard, Hans, Sørensen, Søren Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306380/
https://www.ncbi.nlm.nih.gov/pubmed/30478001
http://dx.doi.org/10.1016/j.ebiom.2018.11.035
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author Wei, Shaodong
Mortensen, Martin Steen
Stokholm, Jakob
Brejnrod, Asker Daniel
Thorsen, Jonathan
Rasmussen, Morten Arendt
Trivedi, Urvish
Bisgaard, Hans
Sørensen, Søren Johannes
author_facet Wei, Shaodong
Mortensen, Martin Steen
Stokholm, Jakob
Brejnrod, Asker Daniel
Thorsen, Jonathan
Rasmussen, Morten Arendt
Trivedi, Urvish
Bisgaard, Hans
Sørensen, Søren Johannes
author_sort Wei, Shaodong
collection PubMed
description 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 COPSAC(2010) 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.
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spelling pubmed-63063802018-12-28 Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial Wei, Shaodong Mortensen, Martin Steen Stokholm, Jakob Brejnrod, Asker Daniel Thorsen, Jonathan Rasmussen, Morten Arendt Trivedi, Urvish Bisgaard, Hans Sørensen, Søren Johannes EBioMedicine Research paper 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 COPSAC(2010) 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. Elsevier 2018-11-23 /pmc/articles/PMC6306380/ /pubmed/30478001 http://dx.doi.org/10.1016/j.ebiom.2018.11.035 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Wei, Shaodong
Mortensen, Martin Steen
Stokholm, Jakob
Brejnrod, Asker Daniel
Thorsen, Jonathan
Rasmussen, Morten Arendt
Trivedi, Urvish
Bisgaard, Hans
Sørensen, Søren Johannes
Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title_full Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title_fullStr Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title_full_unstemmed Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title_short Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
title_sort short- and long-term impacts of azithromycin treatment on the gut microbiota in children: a double-blind, randomized, placebo-controlled trial
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306380/
https://www.ncbi.nlm.nih.gov/pubmed/30478001
http://dx.doi.org/10.1016/j.ebiom.2018.11.035
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