Intestinal fungal dynamics and linkage to hematopoietic cell transplantation outcomes

Allogeneic hematopoietic cell transplantation (allo-HCT) induces profound shifts in the intestinal bacterial microbiota. The dynamics of intestinal fungi and their impact on clinical outcomes have not yet been integrated into a model of microbiota function during allo-HCT. Here, we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing, and fungal cultures to reveal striking trans-kingdom dynamics and their association with patient outcomes. We saw that the overall density and the biodiversity of intestinal fungi were stable during allo-HCT, but the species composition changed drastically from day to day. We identified a subset of patients with fungal dysbiosis characterized by culture positivity, stable expansion of Candida parapsilosis complex species, and distinct trans-kingdom microbiota profiles. These patients had worse overall survival and higher transplant-related mortality independent of candidemia. Our data expand the clinical significance of the mycobiota and suggest that targeting fungal dysbiosis may help to improve long-term patient survival.