Faculty of Dentistry, National University of Singapore, Singapore.
Faculty of Dentistry, National University of Singapore, Singapore.
Arch Oral Biol. 2019 May;101:51-56. doi: 10.1016/j.archoralbio.2019.03.008. Epub 2019 Mar 14.
To determine if commensal oral microflora impacts the severity of chemotherapy-induced oral mucositis (OM).
Specific-pathogen-free (SPF) and germ-free Swiss Webster mice in the experimental groups were dosed with 5-fluorouracil (5-FU) to induce OM. Mice in the control group received phosphate buffered saline. Comparative analyses of the epithelial thickness and cell proliferation/turnover rates, as well as the expression levels of metalloproteinases and pro-inflammatory mediators in the oral mucosa between the control and experimental groups were determined by histopathological and immunohistochemical analyses.
5-FU-treated SPF and germ-free mice showed characteristic features of OM with reduced oral epithelial thickness, presence of inflammatory cells in the connective tissues, and increased levels of expression of metalloproteinases and pro-inflammatory cytokines compared to the respective control groups. When 5-FU-treated SPF and germ-free mice were compared, 5-FU-treated germ-free mice exhibited less severe epithelial destruction with higher expression of the cell proliferation marker Ki67, coupled with lower expression levels of metalloproteinases and pro-inflammatory cytokine in the oral mucosa.
This study provides the first histopathological evidence that oral flora has a detrimental effect on chemotherapy-induced OM in vivo.
确定共生口腔微生物群是否会影响化疗引起的口腔粘膜炎（OM）的严重程度。
实验组的特定病原体（SPF）和无菌瑞士 Webster 小鼠用 5-氟尿嘧啶（5-FU）进行给药以诱导 OM。对照组的小鼠接受磷酸盐缓冲盐水。通过组织病理学和免疫组织化学分析，比较对照组和实验组之间口腔粘膜上皮厚度和细胞增殖/周转率以及金属蛋白酶和促炎介质表达水平的差异。
与各自的对照组相比，5-FU 处理的 SPF 和无菌小鼠表现出 OM 的特征性特征，口腔上皮厚度降低，结缔组织中有炎症细胞，以及金属蛋白酶和促炎细胞因子的表达水平增加。与 5-FU 处理的 SPF 小鼠相比，5-FU 处理的无菌小鼠表现出较轻的上皮破坏，细胞增殖标志物 Ki67 的表达更高，同时口腔粘膜中的金属蛋白酶和促炎细胞因子的表达水平更低。
本研究首次提供了组织病理学证据，表明口腔菌群对体内化疗引起的 OM 有不利影响。
