Development of an oral mucosa model to study host-microbiome interactions during wound healing

Crosstalk between the human host and its microbiota is reported to influence various diseases such as mucositis. Fundamental research in this area is however complicated by the timeframe restrictions during which microbe-host interactions can be studied in vitro. The model proposed in this paper consists of an oral epithelium and biofilm to study microbe-host crosstalk in vitro in non-infectious conditions up to 72 h. Microbiota derived from oral swabs were cultured on an agar/mucin layer and challenged with monolayers of keratinocytes grown on plastic or collagen type I layers embedded with fibroblasts. The overall microbial biofilm composition in terms of species diversity remained representative for the oral microbiome, whilst the epithelial cell morphology and viability were unaffected. Applying the model to investigate wound healing revealed a reduced healing of 30% in presence of microbiota, which was not caused by a reduction of the proliferation index (52.1–61.5) or a significantly increased number of apoptotic (1-1.13) or necrotic (32-30.5%) cells. Since the model allows the separate study of the microbial and cellular exometabolome, the biofilm and epithelial characteristics after co-culturing, it is applicable for investigations within fundamental research and for the discovery and development of agents that promote wound healing.