Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial
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Wei S, Mortensen MS, Stokholm J, Brejnrod AD, Thorsen J, Rasmussen MA, Trivedi U, Bisgaard H, Sørensen SJ
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.
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Curated date: 2021/09/16
Revision editor(s): WikiWorks753, LGeistlinger, Gina
- Location of subjects
- Host species Species from which microbiome was sampled (if applicable)
- 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
- 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
- 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
- Group 1 sample size Number of subjects in the case (exposed) group
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- none mentioned
- Sequencing type
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Statistical test
- Linear Regression
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Shannon Estimator of species richness and species evenness: more weight on species richness
- Richness Number of species
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
|uncultured Bifidobacterium sp.|
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
Revision editor(s): Gina
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