近日，美国加州大学旧金山分校T. Doan课题通过阿奇霉素分布的随机试验阐明了MORDOR I实验改变了人群肠道微生物群。该项研究成果发表在2019年9月出版的《自然—医学》上。

研究人员检测了来自30个尼日尔地区学龄前儿童的肠道微生物组，他们被随机分配并进行一年两次的阿奇霉素或安慰剂服用。肠道微生物组γ-多样性没有显着改变（P = 0.08），但在24个月的随访中，阿奇霉素治疗的儿童中两种弯曲杆菌以及另外33种肠道细菌的相对丰度显着降低。宏基因组分析揭示了治疗组之间肠道细菌的功能差异。 Resistome分析显示，阿奇霉素处理的人群中肠道菌群中大环内酯类抗性基因表达增加（P = 0.004）。这些结果表明，延长阿奇霉素使用时间和用量以降低儿童死亡率可减少某些肠道细菌，包括已知的病原体，但同时抗生素耐药性也增强。

据悉，在尼日尔、马拉维和坦桑尼亚进行的MORDOR I试验表明，向学龄前儿童使用大量阿奇霉素可降低儿童死亡率。然而，大规模但简单的试验并未阐明其所涉及的机制。

附：英文原文

Title: Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution

Author: T. Doan, A. Hinterwirth, L. Worden, A. M. Arzika, R. Maliki, A. Abdou, S. Kane, L. Zhong, S. L. Cummings, S. Sakar, C. Chen, C. Cook, E. Lebas, E. D. Chow, I. Nachamkin, T. C. Porco, J. D. Keenan, T. M. Lietman

Issue&Volume: Volume 25 Issue 9

Abstract: The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. 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 -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. Mass antibiotic administration to preschool children in Nigerien communities alters the relative abundances of 35 bacterial species in the gut microbiome, including enteric pathogens, but also increases expression of macrolide resistance genes.

DOI: 10.1038/s41591-019-0533-0

Source:https://www.nature.com/articles/s41591-019-0533-0