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Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut.
Nature Ecology & Evolution ( IF 13.9 ) Pub Date : 2020-07-06 , DOI: 10.1038/s41559-020-1236-0
Kern Rei Chng 1 , Tarini Shankar Ghosh 1, 2 , Yi Han Tan 3 , Tannistha Nandi 1 , Ivor Russel Lee 3 , Amanda Hui Qi Ng 1 , Chenhao Li 1 , Aarthi Ravikrishnan 1 , Kar Mun Lim 1 , David Lye 3, 4, 5, 6 , Timothy Barkham 6 , Karthik Raman 7, 8, 9 , Swaine L Chen 1 , Louis Chai 3, 10 , Barnaby Young 4, 5, 6 , Yunn-Hwen Gan 3 , Niranjan Nagarajan 1, 3
Affiliation  

Loss of diversity in the gut microbiome can persist for extended periods after antibiotic treatment, impacting microbiome function, antimicrobial resistance and probably host health. Despite widespread antibiotic use, our understanding of the species and metabolic functions contributing to gut microbiome recovery is limited. Using data from 4 discovery cohorts in 3 continents comprising >500 microbiome profiles from 117 individuals, we identified 21 bacterial species exhibiting robust association with ecological recovery post antibiotic therapy. Functional and growth-rate analysis showed that recovery is supported by enrichment in specific carbohydrate-degradation and energy-production pathways. Association rule mining on 782 microbiome profiles from the MEDUSA database enabled reconstruction of the gut microbial ‘food web’, identifying many recovery-associated bacteria as keystone species, with the ability to use host- and diet-derived energy sources, and support repopulation of other gut species. Experiments in a mouse model recapitulated the ability of recovery-associated bacteria (Bacteroides thetaiotaomicron and Bifidobacterium adolescentis) to promote recovery with synergistic effects, providing a boost of two orders of magnitude to microbial abundance in early time points and faster maturation of microbial diversity. The identification of specific species and metabolic functions promoting recovery opens up opportunities for rationally determining pre- and probiotic formulations offering protection from long-term consequences of frequent antibiotic usage.



中文翻译:

宏基因组关联分析确定了肠道中抗生素后生态恢复的微生物决定因素。

在抗生素治疗后,肠道微生物群多样性的丧失会持续很长时间,从而影响微生物群功能、抗菌素耐药性,并可能影响宿主健康。尽管广泛使用抗生素,但我们对有助于肠道微生物组恢复的物种和代谢功能的理解是有限的。使用来自 3 个大陆的 4 个发现队列的数据,包括来自 117 个人的 >500 个微生物组谱,我们确定了 21 种细​​菌,它们与抗生素治疗后的生态恢复密切相关。功能和生长速率分析表明,特定碳水化合物降解和能量产生途径的富集支持恢复。对来自 MEDUSA 数据库的 782 个微生物组谱进行关联规则挖掘,能够重建肠道微生物“食物网”,将许多与恢复相关的细菌确定为关键物种,具有使用宿主和饮食衍生能源的能力,并支持其他肠道物种的重新繁殖。在小鼠模型中的实验概括了恢复相关细菌的能力(Bacteroides thetaiotaomicronBifidobacteriumteenis)以协同效应促进恢复,在早期时间点将微生物丰度提高两个数量级,并加快微生物多样性的成熟。对促进恢复的特定物种和代谢功能的鉴定为合理确定益生菌制剂和益生菌制剂提供了机会,这些制剂可防止频繁使用抗生素的长期后果。

更新日期:2020-07-06
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