Recovery of gut microbiota of healthy adults following antibiotic exposure

Recovery of gut microbiota of healthy adults following antibiotic exposure
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DOI:
10.1038/s41564-018-0257-9
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发表时间:
2018-11-01
影响因子:
28.3
通讯作者:
Pedersen, Oluf
Pedersen, Oluf
中科院分区:
生物学1区
文献类型:
--
作者:
Palleja, Albert;Mikkelsen, Kristian H.;Pedersen, Oluf

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为了尽量减少抗生素的影响,肠道微生物携带和交换抗生素抗性基因,统称为它们的抗性组。使用基于散弹枪测序的宏基因组学,我们分析了12名健康男性在6个月的时间里,在使用3种最后手段抗生素(美罗培南、庆大霉素和万古霉素)鸡尾酒治疗4天后,肠道微生物群的部分根除和随后的再生。最初的变化包括肠杆菌和其他病原体的大量繁殖,如粪肠球菌和核梭杆菌,以及双歧杆菌和丁酸盐产生菌的减少。受试者的肠道微生物群在1.5个月内恢复到接近基线的组成,尽管在治疗前所有受试者中存在的9种常见物种在180天后在大多数受试者中仍未检测到。在干预期间和干预后,积极选择含有β -内酰胺抗性基因的物种。含有糖肽或氨基糖苷抗性基因增加了重新定植的几率,然而,前者也降低了生存的几率。体内抗生素干预下的成分变化与体外药敏试验的结果相匹配。尽管抗生素暴露后会留下轻微但持久的印记,但健康年轻人的肠道微生物群对短期广谱抗生素干预具有弹性,其抗生素耐药基因的携带调节了其恢复过程。
To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 lastresort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour beta-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.