An increase in Fusobacterium is associated with the severity of oral mucositis after radiotherapy

Abstract

Radiotherapy is a common treatment for head and neck cancer but often causes oral mucositis, which reduces quality of life. Recent studies suggest that radiotherapy affects the oral microbiota, but whether it contributes to the severity of mucositis has been unclear. This study investigated the association between radiotherapy-induced changes in the oral microbiota and the severity of mucositis using 16 S rRNA gene sequencing. Oral samples were collected before, during, and after radiotherapy and were analyzed for changes in bacterial composition and diversity using the Shannon index and Chao1 index. Severity of mucositis was assessed, and its association with changes in bacterial groups was investigated. In total, 43 patients participated in the study. Fusobacterium was significantly increased in the group with severe mucositis (p = 0.020), with an occupancy rate of more than 7% after radiotherapy and a positive correlation with severity of mucositis (p = 0.042). There was a significant increase in the Chao1 index after radiotherapy (p = 0.001) but not in the Shannon index. Changes in oral microbiota may determine the severity of radiotherapy-induced mucositis. An increase in Fusobacterium was found to be closely associated with the severity of mucositis and should be controlled to prevent radiotherapy-induced mucositis in head and neck cancer patients.

Keywords: Fusobacterium; 16S rRNA gene sequencing; Head and neck cancer; Inflammation; Oral microbiota; Oral mucositis; Radiotherapy.

Fig. 1

Changes in the composition of the oral microbiota in 43 patients undergoing radiotherapy for head and neck cancer. The stacked bar chart compares the changes pre-, mid-, and post-radiotherapy. Each bar represents the average relative abundance of the various groups of bacteria at the genus level color-coded by genus.

Fig. 2

Changes in the alpha diversity of the oral microbiota at pre-, mid-, and post-radiotherapy evaluated using the Shannon index and Chao1 index. The Chao1 index values were significantly greater mid- and post-radiotherapy compared with those pre-radiotherapy (p < 0.05). There was no statistically significant difference in the Shannon index value between pre-, mid-, and post-radiotherapy. *p < 0.05.

Fig. 3

Comparison of average relative abundances of the major oral flora at three time points (pre-, mid-, and post-radiotherapy) between patients with mild mucositis and those with severe mucositis. The bar graph shows the average relative abundances of the major oral flora in patients according to whether mucositis was mild (blue) or severe (orange). The error bars represent the standard deviation. Only genera with statistically significant differences are shown. * p < 0.05.

Fig. 4

Extent of change in the average relative abundance of the major oral flora at the genus level pre- and post-radiotherapy. The box plot shows significant increases in Fusobacterium, Capnocytophaga, Leptotrichia, and Parvimonas and decreases in Veillonella and Lactobacillus in the severe group (orange) compared with those in the mild group (blue) (p < 0.05).

Fig. 5

Associations between the extent of change in the average relative abundances of specific genera and the severity of oral mucositis pre- and post-radiotherapy. Spearman’s rank correlation coefficient analysis revealed significant positive correlations for Fusobacterium, Capnocytophaga, Leptotrichia, and Parvimonas (p < 0.05) and significant negative correlations for Veillonella and Lactobacillus (p < 0.05) with the severity of mucositis.