摘要

为了最大限度地减少抗生素的影响，肠道微生物拥有并交换抗生素抗性基因，统称为抵抗组织。使用基于鸟枪测序的宏基因组学，我们分析了12个健康男性的肠道微生物群的部分根除和随后的再生长，为期4天的干预后，使用3种最后抗生素的混合物：美罗培南，庆大霉素和万古霉素。最初的变化包括肠杆菌和其他病菌的大量繁殖，如粪肠球菌和核梭杆菌，以及双歧杆菌和丁酸盐生产者的消耗。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，尽管在治疗之前存在于所有受试者中的9种常见物种在180天后仍然在大多数受试者中检测不到。在干预期间和之后，选择具有β-内酰胺抗性基因的物种。携带糖肽或氨基糖苷类抗性基因增加了从头定植的可能性，然而，前者也降低了存活几率。体内抗生素干预下的组成变化与体外药敏试验的结果相匹配。尽管抗生素接触后存在温和而持久的印记，但健康年轻成年人的肠道微生物群对短期广谱抗生素干预具有弹性，其抗生素抗性基因携带调节其恢复过程。

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 last-resort 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 β-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.

https://www.ncbi.nlm.nih.gov/pubmed/30349083