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

Abstract

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- and post-HSCT. Transplantation was associated with a decrease in oral α diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graft-versus-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.

• Authors: 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
• Journal: Blood advances (Blood Adv) Vol. 4 Issue 13 Pg. 2912-2917 (07 14 2020) ISSN: 2473-9537 [Electronic] United States
• PMID: 32598476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Topics

• Gastrointestinal Microbiome
• Graft vs Host Disease (etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Microbiota
• Stomatitis (etiology)