Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance.
Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance.
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肾移植患者的尿液微生物组揭示了生态失调，可能存在抗生素耐药性。
DOI：
10.1016/j.trsl.2016.08.008
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Perkins,DavidL
中科院分区：
文献类型：
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作者：
Rani,Asha;Ranjan,Ravi;McGee,HalvorS;Andropolis,KalistaE;Panchal,DiptiV;Hajjiri,Zahraa;Brennan,DanielC;Finn,PatriciaW;Perkins,DavidL
最近的研究已经确定，一个复杂的微生物群落定殖人类尿路;然而，它们在肾移植患者预防性抗生素治疗中的作用仍然研究不足。我们的目的是调查肾移植受者的尿液微生物组。收集了21名肾移植患者和8名健康对照的尿液样本。所有患者均接受抗生素联合甲氧苄啶-磺胺甲恶唑预防性治疗。从尿液样品中分离宏基因组DNA，使用鸟枪测序方法在Illumina HiSeq 2000平台上测序，并分析微生物分类和功能注释。我们的研究结果表明，肾移植患者的尿液微生物组在从门到种的所有分类水平上都有显著差异，与健康对照组相比，微生物多样性降低，潜在致病物种的丰度增加。具体来说，在门的水平上，我们检测到由于粪肠球菌的增加，放线菌门的数量显著减少，厚壁菌门的数量增加。此外，由于大肠杆菌的增加，变形菌门的数量增加。对尿宏基因组的预测功能的分析显示，叶酸途径中的酶的丰度增加，包括不受甲氧苄啶-磺胺甲恶唑抑制的二氢叶酸合酶，但可以增强叶酸代谢。本报告使用鸟枪宏基因组学方法表征肾移植的尿液微生物组。我们的研究结果表明，在预防性抗生素的背景下，尿液微生物群可能会发生改变，这表明治疗性干预可能会使尿液微生物群转向选择对抗生素耐药性增加的细菌物种。评价和开发不促进抗生素耐药性的最佳预防方案是未来的一个重要目标。
Recent studies have established that a complex community of microbes colonize the human urinary tract; however, their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients after kidney transplantation and 8 healthy controls were collected. All patients received prophylactic treatment with the antibiotic combination trimethoprim-sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using shotgun sequencing approach on Illumina HiSeq 2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity, and increased abundance of potentially pathogenic species compared with healthy controls. Specifically, at the phylum level, we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases inEnterococcus faecalis.In addition, there was an increase in the Proteobacteria due to increases inEscherichia coli.Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim-sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased resistance to antibiotics. The evaluation and development of optimal prophylactic regimens that do not promote antibiotic resistance is an important future goal.