Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients

Abstract

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.

Figure 1

PCA on oral microbiome profiles by time point, (A) cases without ulcerative oral mucositis and (B) cases who developed ulcerative oral mucositis. Boxes indicate MEDs that contributed most to PC1. Left box: more abundant at low values of PC1, right box: more abundant at high values of PC1.

Figure 2

Diversity of oral microbiome profiles per group by time point, (A) Shannon index, (B) Dominance index. Lines connect significantly different time points (GLM RM test, p < 0.01).

Figure 3

MEDs that significantly discriminated the two groups –patients that did not develop ulcerative oral mucositis (green) and patients that did develop ulcerative oral mucositis (red) before autoSCT (biomarker identification tool LEfSe, p < 0.05, LDA > 2).

Figure 4

Relative abundance of fungi in the samples of patients who did and did not develop ulcerative oral mucositis (A) before autoSCT, (B) 0–4 days after autoSCT, (C) one week, (D) two weeks, (E) three months after autoSCT. Bar connects significant differences (Mann Whitney U test). Fungi were detected using primers from Vollmer et al..

Figure 5

PCA of salivary microbial profiles, colored by fungal load relative to bacterial DNA (16S rDNA). Microbiome of samples with 0.1% fungi or higher (red) differed significantly from those with no fungi (green) (F = 3.106, p < 0.05, PERMANOVA). The boxes indicate the MEDs that were associated with high fungal load (left box) or low fungal load (right box), based on PC1 loadings.

Figure 6

Study flow diagram.