High-resolution mycobiota analysis reveals dynamic intestinal translocation prior to invasive candidiasis

High-resolution mycobiota analysis reveals dynamic intestinal translocation prior to invasive candidiasis
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高分辨率真菌群分析揭示了侵袭性念珠菌病之前的动态肠道易位

DOI:
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发表时间:
2019
期刊:
Nature Network Boston
影响因子:
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通讯作者:
T. Hohl
T. Hohl
中科院分区:
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文献类型:
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作者:
B. Zhai;M. Ola;T. Rolling;T. Rolling;N. Tosini;Sari Joshowitz;E. Littmann;L. Amoretti;E. Fontana;R. Wright;Edwin Miranda;Charlotte A. Veelken;S. Morjaria;S. Morjaria;J. Peled;J. Peled;M. Brink;M. Brink;N. Babady;G. Butler;Y. Taur;Y. Taur;T. Hohl;T. Hohl

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肠道菌群是一个由细菌、古细菌、病毒、原生生物和真菌组成的复杂群落1,2。虽然细菌成分的组成与免疫稳态和感染易感性有关3 - 7,但非细菌成分和跨界微生物相互作用在这些过程中的作用知之甚少2,8。尽管肠道真菌(即真菌菌群)与真菌血流感染的关系尚不明确,但真菌是免疫功能低下个体感染性发病率和死亡率的主要原因。我们将优化的生物信息学管道与高分辨率真菌群测序和来自异基因造血细胞移植接受者的粪便和血液标本的比较基因组分析相结合。念珠菌血流感染的患者既往有明显的致病性念珠菌肠道扩张;这种扩张是由多物种和亚种之间的复杂动态组成的,具有进入血液的随机易位模式。致病性念珠菌的肠道扩张与细菌负担和多样性的大量损失有关,特别是厌氧菌。因此,肠道真菌和细菌的同时分析确定了跨王国的生态失调状态,这些状态可能促进真菌易位并促进侵袭性疾病。这些发现支持微生物群驱动的方法来识别有真菌血流感染风险的患者,以进行先发制人的治疗干预。在造血细胞移植受者中,致病性念珠菌种类的扩增与肠道细菌生态失调相结合,先于念珠菌血流感染。
The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi 1 , 2 . Although the composition of bacterial constituents has been linked to immune homeostasis and infectious susceptibility 3 – 7 , the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood 2 , 8 . Fungi represent a major cause of infectious morbidity and mortality in immunocompromised individuals, although the relationship of intestinal fungi (that is, the mycobiota) with fungal bloodstream infections remains undefined 9 . We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant. Patients with Candida bloodstream infection experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida spp. was associated with a substantial loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk of fungal bloodstream infections for pre-emptive therapeutic intervention. Expansion of pathogenic Candida species coupled with bacterial dysbiosis in the gut precedes Candida bloodstream infections in hematopoietic cell transplant recipients.
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