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阿莫西林单疗程给药对小鼠肠道微生物群和耐药组的长期破坏,以及菊粉、长双歧杆菌和粪便微生物群移植的恢复作用。

The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.

机构信息

College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin, 300350, China.

College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin, 300350, China; Hebei Key Laboratory of Air Pollution Cause and Impact (preparatory), College of Energy and Environmental Engineering, Hebei University of Engineering, Handan, 056038, China.

出版信息

Environ Pollut. 2020 Oct;265(Pt A):114651. doi: 10.1016/j.envpol.2020.114651. Epub 2020 Apr 23.

Abstract

The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.

摘要

在治疗病原性感染时使用抗生素会改变肠道微生物组和相关的抗药组,对人类健康造成长期的不利影响。在这项研究中,用模拟人类的方案对小鼠进行了为期七天的 25.0mg/kg 阿莫西林治疗,分别用 16S rRNA 扩增子测序和高通量 qPCR 来描述肠道微生物组和抗药组。同时,分析了菊粉、长双歧杆菌(B. longum)和粪便微生物移植(FMT)的单独应用后长达 35 天的菌群恢复情况。结果表明,单次 AMX 暴露对小鼠肠道微生物组和抗药组的负面影响持续时间较长。具体而言,Klebsiella 和 Escherichia-Shigella 等条件致病菌显著富集,而双歧杆菌和乳杆菌等益生菌显著减少。此外,阿莫西林暴露后β-内酰胺耐药基因和外排耐药基因明显富集。与长双歧杆菌相比,FMT 和菊粉通过分别重建微生物群落和刺激特定的益生菌来更好地恢复肠道微生物组。微生物组的这种变化导致它们对抗药组变化的缓解效果不同。菊粉对 AMX 诱导的 ARG 丰度和多样性富集的消除效果最佳。FMT 和长双歧杆菌引起特定 ARGs 的去除,如 ndm-1 和 blaPER。网络分析表明,大多数 ARGs 容易被 Firmicutes 和 Proteobacteria 携带。总的来说,肠道抗药组的变化部分与细菌群落结构的变化以及转座酶和整合子有关。综上所述,单次阿莫西林治疗后,肠道微生物组和抗药组发生了深刻的破坏,而菊粉、长双歧杆菌和 FMT 的不同恢复方式对其有一定的缓解作用。

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