Host-microbe interactions in chemotherapy-induced oral mucositis

Introduction : More and more evidence is emerging that microbiota are involved in the development and severity of oral mucositis. It is known that the microbiome is changed during mucositis and that chemotherapy is often complicated with local and even systemic infections. But still little is known about the role of oral commensals in the onset, development, and duration of oral mucositis. Objectives : We want to explore the role of host-microbe interactions in chemotherapy-induced oral mucositis by means of an in-house developed in vitro model. Methods : The model consists of a 24-well TranswellTM plate with removable inserts in which a reconstructed biofilm, derived from an oral swab or saliva of cancer patients or healthy donors, is co-cultured with epithelial monolayer cells in presence or absence of chemotherapeutics. A wound scratch assay is performed to evaluate the effect of microbiota on the healing of epithelial cells exposed to chemotherapeutics. Results : We show that oral microbiota have an overall negative impact on wound closure of oral epithelial cells, irrespective of the presence of chemotoxic agents. Quantification of the biofilm cell numbers showed that the effect of 5-FU varied according to the type of oral sample used and that there is interindividual variability. We further show shifts in the microbial community of the reconstructed biofilm after chemotherapy treatment. Discussion : Our in vitro mucositis model is able to identify functional and mechanistic changes in host-microbe interactions. This will help us to further characterise the pathobiology of mucositis and to develop new treatment strategies