Longitudinal analysis at three oral sites links oral microbiota to clinical outcomes in allogeneic hematopoietic stem-cell transplant

Abstract

ABSTRACT Allogeneic hematopoietic stem-cell transplant (allo-HSCT) is potentially curative for several hematological disorders. Before stem-cell infusion, recipients undergo a conditioning regimen with chemo/radiotherapy and immunosuppressants, requiring the use of antibiotics to treat and prevent infections. This regimen promotes drastic alterations in the recipient’s microbiota, including the oral microbiota, which have been associated with allo-HSCT complications and poor outcomes. However, long-term longitudinal studies on the oral microbiota of allo-HSCT recipients are scarce and disregard the existence of distinct microbiota within the oral cavity. Here, we used 16S rRNA gene sequencing to characterize the longitudinal microbiota dynamics in a prospective cohort of 31 allo-HSCT recipients at three oral sites (gingival crevicular fluid, oral mucosa, and supragingival biofilm). We found declines in bacterial diversity and major shifts in microbiota composition in all oral sites during allo-HSCT, including blooms of potentially pathogenic genera. These blooms in some cases preceded respiratory infections caused by the blooming bacteria. We also noticed that differences in microbiota composition between oral sites were lost during allo-HSCT. Overall, after allo-HSCT, the distinct oral microbiota returned to their preconditioning state, although at variable levels of competence per patient. After stratifying patients based on recovery levels, we found that recoverers of the oral mucosa microbiota composition had earlier reconstitution of normal blood leukocyte counts. Most notably, oral mucosa microbiota recovery was an independent biomarker of better allo-HSCT outcomes. This study highlights the potential clinical impact of the oral microbiota in the allo-HSCT setting and the clinical value of tracking oral microbiota changes during allo-HSCT. IMPORTANCE The oral cavity is the ultimate doorway for microbes entering the human body. We analyzed oral microbiota dynamics in allogeneic hematopoietic stem-cell transplant recipients and showed that microbiota injury and recovery patterns were highly informative on transplant complications and outcomes. Our results highlight the importance of tracking the recipient’s microbiota changes during allogeneic hematopoietic stem-cell transplant to improve our understanding of its biology, safety, and efficacy.

Keywords

• oral microbiome
• 16S rRNA gene sequencing
• allogeneic hematopoietic cell transplant
• microbiome stability
• blooming of bacteria
• biomarkers