Department of Biology, Section of Microbiology, University of Copenhagen, Universitetsparken 15, bldg. 1, DK2100, Copenhagen, Denmark.
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Alle 34, 2820 Gentofte, Denmark.
EBioMedicine. 2018 Dec;38:265-272. doi: 10.1016/j.ebiom.2018.11.035. Epub 2018 Nov 23.
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.
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 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.
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.
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.
大环内酯类抗生素常用于治疗儿童呼吸道感染和哮喘样发作。虽然其临床疗效已得到证实，但人们对其治疗作用的副作用仍存在担忧。本研究旨在评估阿奇霉素短期和长期使用对幼儿肠道微生物群的影响。
我们对 COPSAC 队列中诊断为反复出现哮喘样症状的 12-36 月龄儿童进行了一项随机、双盲、安慰剂对照试验。每个急性哮喘样发作均随机接受为期 3 天的每日 10mg/kg 阿奇霉素口服液或安慰剂治疗。阿奇霉素将发作持续时间缩短了一半，这是主要终点，之前已有报道。本研究报告了治疗后肠道微生物群的评估结果，这是次要终点。在随机分组后 14 天（N=59，短期）和 4 岁时（N=49，长期，其中 N=18 接受安慰剂治疗）收集粪便样本，并通过 16S rRNA 基因扩增子测序进行分析。
短期治疗后，阿奇霉素组观察到丰富度降低了 23%，Shannon 多样性降低了 13%。微生物群组成主要发生在放线菌门，特别是双歧杆菌属的丰度降低。长期（治疗后 13-39 个月），阿奇霉素组和安慰剂组的肠道微生物群组成无差异。
阿奇霉素治疗后 14 天引起肠道微生物群紊乱，但对肠道微生物群组成无长期影响。然而，应注意的是，我们的分析中在 4 岁时接受安慰剂治疗的儿童中，粪便样本数量有限。
Lundbeck 基金会、丹麦卫生部、丹麦战略研究理事会、首都地区研究基金会、中国国家留学基金委。
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