Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution.
Thuy A DoanA HinterwirthL WordenA M ArzikaR MalikiA AbdouS KaneL ZhongS L CummingsS SakarC ChenC CookE LebasEric D ChowI NachamkinT C PorcoJeremy David KeenanT M LietmanPublished in: Nature medicine (2019)
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 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.
Keyphrases
- early life
- phase iii
- gene expression
- phase ii
- clinical trial
- double blind
- study protocol
- open label
- cardiovascular events
- placebo controlled
- mental health
- dna methylation
- antimicrobial resistance
- young adults
- randomized controlled trial
- coronary artery disease
- single cell
- risk factors
- cardiovascular disease
- biofilm formation
- newly diagnosed
- gram negative
- escherichia coli
- replacement therapy
- combination therapy
- liquid chromatography
- molecularly imprinted
- genetic diversity
- anaerobic digestion