Hematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species

Abstract

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 during allo-HCT are not fully understood. Here, we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing, and fungal cultures of 1279 fecal samples from a cohort of 156 allo-HCT patients to reveal potential 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 defined by culture positivity (n=53) and stable expansion of Candida parapsilosis complex species (n=19). They presented with distinct trans-kingdom microbiota profiles, characterized by a decreased intestinal bacterial biomass. These patients had worse overall survival and higher transplant-related mortality independent of candidemia. This expands our understanding of the clinical significance of the mycobiota and suggests that targeting fungal dysbiosis may help to improve long-term patient survival.