Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic-HSCT, partially accounting for the variability in OM severity. Using 16S rRNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre and post-HSCT. Pre-HSCT, Kingella, and Atopobium abundance correlated with future development of severe OM. Post-transplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes during the week following HSCT, compared to patients with no or mild OM. Changes in specific metabolites were well- explained by microbial composition and the common metabolic pathway was the polyamines pathway, which is essential for epithelial homeostasis. Together, our findings suggest that salivary microbial composition and associated metabolites are associated with the development of OM and may offer new avenues of intervention.