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^3,4,5,6,7, 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 undefined⁹. 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.

肠道微生物群是由细菌、古细菌、病毒、原生生物和真菌组成的复杂群落^1,2。尽管细菌成分的组成与免疫稳态和感染易感性^3,4,5,6,7有关，但人们对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。真菌是免疫功能低下个体感染发病率和死亡率的主要原因，尽管肠道真菌（即真菌菌群）与真菌血流感染的关系仍未确定⁹. 我们将优化的生物信息学管道与高分辨率真菌生物群测序和来自同种异体造血细胞移植受者的粪便和血液样本的比较基因组分析相结合。患有念珠菌血流感染的患者之前曾经历过致病性念珠菌的显着肠道扩张；这种扩张包括多个物种和亚种之间的复杂动态，具有随机易位模式进入血流。致病性念珠菌的肠道扩张spp. 与细菌负担和多样性的大量损失有关，特别是在厌氧菌中。因此，对肠道真菌和细菌的同时分析确定了可能促进真菌易位和促进侵袭性疾病的菌群失调状态。这些发现支持微生物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。