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

Roni Shouval, Adi Eshel, Bar Dubovski, Amir A. Kuperman, Ivetta Danylesko, Joshua A. Fein, Shalev Fried, Mika Geva, Elizaveta Kouniavski, Hadar Neuman, Ayelet Armon-Omer, Radi Shahien, Efrat Muller, Cecilia Noecker, Elhanan Borenstein, Yoram Louzoun, Arnon Nagler, Omry Koren

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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 ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- A nd post-HSCT. Transplantation was associated with a decrease in oral a diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graftversus-host disease prophylaxis pre-HSCT, Kingella and Atopobium abundance correlated with future development of severe OM. Posttransplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes post-HSCT, compared with 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 metabolites are associated with the development of OM, offering new insights on pathophysiology and potential avenues of intervention.

Original languageEnglish
Pages (from-to)2912-2917
Number of pages6
JournalBlood advances
Issue number13
StatePublished - 14 Jul 2020

Bibliographical note

Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.


  • Are associated with mucositis development
  • Dysbiosis of the oral microbiome with flourishment of pathobionts are accentuated in patients undergoing hsct with oral mucositis.
  • Key points
  • Salivary microbial composition and associated metabolites
  • Specifically the polyamine pathway


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