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High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis

Authors :
Tobias M. Hohl
Eric R. Littmann
Charlotte A Veelken
Emily Fontana
Roberta J. Wright
N. Esther Babady
Marcel R.M. van den Brink
Geraldine Butler
Edwin Miranda
Jonathan U. Peled
Sejal Morjaria
Thierry Rolling
Sari Joshowitz
Nicholas L. Tosini
Ying Taur
Luigi A Amoretti
Bing Zhai
Mihaela Ola
Source :
Nature Medicine. 26:59-64
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

Abstract

The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi1,2. Although the composition of bacterial constituents has been linked to immune homeostasis and infectious susceptibility3-7, the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood2,8. 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.

Details

ISSN :
1546170X and 10788956
Volume :
26
Database :
OpenAIRE
Journal :
Nature Medicine
Accession number :
edsair.doi.dedup.....1cd19466968a55d75c8eaeb04f138ba9