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

Study information

Needs review

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

30478001

DOI Digital object identifier for electronic documents.

10.1016/j.ebiom.2018.11.035

URI

Authors

Wei S, Mortensen MS, Stokholm J, Brejnrod AD, Thorsen J, Rasmussen MA, Trivedi U, Bisgaard H, Sørensen SJ

Journal

EBioMedicine

Year

2018

Keywords:

Antibiotics, Asthma, Azithromycin, Children, Gut microbiota, RCT

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.

Experiment 1

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2021/09/16

Curator: Gina

Revision editor(s): WikiWorks, LGeistlinger, Gina, Victoria

Subjects

Location of subjects: Denmark

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Azithromycin (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-11-,10q24.1-q25.1,aritromicina,Azenil,Azifast,Azigram,Azimakrol,azithromycine,azithromycinum,Azitromin,AZM,Hemomycin,InChIKey=MQTOSJVFKKJCRP-BICOPXKEBK,Zithromax,Zmax,Azithromycin,azithromycin

Group 0 name Corresponds to the control (unexposed) group for case-control studies: The group given a placebo

Group 1 name Corresponds to the case (exposed) group for case-control studies: The group given an azithromycin oral solution

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: 1-3-year-olds diagnosed with recurrent asthma-like symptoms from the COPSAC2010 cohort. Exclusion criteria included macrolide allergy, heart, liver, neurological, kidney disease, and or one or more clinical signs of pneumonia. Participants were prescribed a 3-day course of oral azithromycin solution of 10mg/kg per day.

Group 0 sample size Number of subjects in the control (unexposed) group: 33

Group 1 sample size Number of subjects in the case (exposed) group: 39

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): none mentioned

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: Linear Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Richness Number of species: decreased

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/09/24

Curator: Gina

Revision editor(s): Gina

Source: Supplementary table 2

Description: Short term effects: the relative abundance of significant taxa between groups at different phylogenetic levels.

Abundance in Group 1: decreased abundance in The group given an azithromycin oral solution

NCBI	Quality Control	Links
Actinomycetota
Bifidobacteriales
Bacillota
Bifidobacteriaceae
uncultured Bifidobacterium sp.

Revision editor(s): Gina

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/09/24

Curator: Gina

Revision editor(s): Gina

Source: Supplementary table 2

Description: Short term effect: the relative abundance of significant taxa between groups at different phylogenetic levels.

Abundance in Group 1: increased abundance in The group given an azithromycin oral solution

NCBI	Quality Control	Links
Lachnospiraceae
Flavonifractor

Revision editor(s): Gina