Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients

Abstract

Stem cell transplantation (SCT) is associated with oral microbial dysbiosis. However, long-term longitudinal data are lacking. Therefore, this study aimed to longitudinally assess the oral microbiome in SCT patients and to determine if changes are associated with oral mucositis and oral chronic graft-versus-host disease. Fifty allogeneic SCT recipients treated in two Dutch university hospitals were prospectively followed, starting at pre-SCT, weekly during hospitalization, and at 3, 6, 12, and 18 months after SCT. Oral rinsing samples were taken, and oral mucositis (WHO score) and oral chronic graft-versus-host disease (NIH score) were assessed. The oral microbiome diversity (Shannon index) and composition significantly changed after SCT and returned to pre-treatment levels from 3 months after SCT. Oral mucositis was associated with a more pronounced decrease in microbial diversity and with several disease-associated genera, such as Mycobacterium, Staphylococcus, and Enterococcus. On the other hand, microbiome diversity and composition were not associated with oral chronic graft-versus-host disease. To conclude, dysbiosis of the oral microbiome occurred directly after SCT but recovered after 3 months. Diversity and composition were related to oral mucositis but not to oral chronic graft-versus-host disease.

Keywords: allogeneic stem cell transplant; conditioning; dysbiosis; oral graft-versus-host disease; oral microbiome; oral mucositis.

Figure 1

Oral microbiome at all time points in the study: (a) Shannon diversity index (boxes show median and whiskers 5–95 percentile). * Marks significant differences compared to pre-SCT (Linear Mixed Model Analysis, p < 0.05); (b) principal component analysis plot. Left box indicates more abundant taxa at low values of the loadings of PC1, right box—at high values.

Figure 2

Shannon diversity index at several time points in patients with and without oral mucositis (boxes show median and whiskers 5-95 percentile). * Marks significant differences compared to the other patient group (Linear Mixed Model Analysis, p < 0.05).

Figure 3

Relative Abundance (percentage) of top 15 most abundant genera at different time points in patients who did not experience oral mucositis (a) and patients who did experience oral mucositis (b).

Figure 4

PCA on oral microbiome over time for patients who did not (a) and did (b) experience oral mucositis; left box more abundant taxa at low values of PC1 loadings; right box more abundant taxa at high values of PC1.

Figure 5

Shannon diversity index at several time points in patients with and without oral GVHD (median, 5–95 percentile). * Marks significant differences compared to pre-SCT (Linear Mixed Model Analysis, p < 0.05).

Figure 6

Principal component analysis on oral microbiome over time for patients who did not (a) and did (b) experience oral GVHD. Left box—more abundant taxa at low values of PC1 loadings, right box—at high values.