Dental plaque microbiota following allogeneic hematopoietic cell transplantation and risk of chronic graft-

Microbiota disruptions have been associated with short-term complications after allogeneic hematopoietic cell transplantation (alloHCT). However, only a few studies have examined the relationship between dysbiosis and chronic graft-versus-host disease (cGvHD), the main long-term immunologic toxicity of alloHCT. Considering the role of oral microbiota in systemic inflammatory diseases, we evaluated whether oral microbiota at day 28 post HCT corresponding to clinical recovery from the acute events after transplantation is associated with subsequent cGvHD. Shotgun metagenomic sequencing of 207 saliva and supragingival plaque samples collected longitudinally at baseline (pre-conditioning), day +28, and day +84 from 37 patients (11 with subsequent moderate/severe cGvHD) revealed a significant association between day +28 plaque microbiota composition and cGvHD. Two orthogonal statistical approaches demonstrated Streptococcus sanguinis and Prevotella loescheii in day +28 plaque to be associated with cGvHD. Metagenome-based functional analysis identified 4 microbial metabolic pathways associated with future cGvHD, 2 of which were highly attributed to S. sanguinis. These pathways - ethanolamine utilization and glycerol metabolism - increase bacterial fitness by providing an alternative carbon/nitrogen source and improving survival in inflamed tissues. Our findings propose a novel mechanism by which the early post-transplant dental biofilm may contribute to cGvHD months later, offering a potential target for early prophylactic intervention.