Francis I Proctor Foundation, University of California, San Francisco, CA, USA.
Department of Ophthalmology, University of California, San Francisco, CA, USA.
Nat Med. 2019 Sep;25(9):1370-1376. doi: 10.1038/s41591-019-0533-0. Epub 2019 Aug 12.
The MORDOR I trial, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.
MORDOR I 试验在尼日尔、马拉维和坦桑尼亚进行，结果表明，大规模给学龄前儿童服用阿奇霉素可降低儿童死亡率。然而，这项规模庞大但设计简单的试验排除了对涉及机制的确定。在这里，我们研究了来自 30 个尼日尔社区的学龄前儿童的肠道微生物组，这些儿童被随机分配接受每年两次的阿奇霉素或安慰剂治疗。肠道微生物组 γ-多样性没有显著改变（P=0.08），但在 24 个月随访时，接受阿奇霉素治疗的儿童中两种弯曲杆菌属物种以及另外 33 种肠道细菌的相对丰度显著降低。宏基因组分析显示治疗组之间肠道细菌的功能存在差异。抗药基因组分析显示，接受阿奇霉素治疗的社区的肠道微生物群中，大环内酯类抗生素耐药基因的表达增加（P=0.004）。这些结果表明，为降低儿童死亡率而长期大规模分发阿奇霉素会减少某些肠道细菌，包括已知的病原体，同时选择抗生素耐药性。
