Biofilm Models to Study the Etiology and Pathogenesis of Oral Diseases.

More than 700 microbial species inhabit the complex environment of the oral cavity. For years microorganisms have been studied in pure cultures, a highly artificial situation because microorganisms in natural habitats grow as complex ecologies, termed biofilms. These resemble multicellular organisms and are characterized by their overall metabolic activity upon multiple cellular interactions. Microorganisms in biofilms express different genes than their planktonic counterparts, resulting in higher resistance to antimicrobials, different nutritional requirements, or creation of a low redox potential allowing the growth of strictly anaerobic bacteria in the presence of oxygen. Multiple in vitro biofilm models have been described in the literature so far. The main emphasis here will be on multispecies biofilm batch culture models developed in Zurich. The standard 6-species supragingival biofilm model has been used to study basic aspects of oral biofilms such as structure, social behavior, and spatial distribution of microorganisms, or diffusion properties. Numerous parameters related to the inhibition of dental plaque were tested illustrating the high reliability of the model to predict the in vivo efficiency of antimicrobials. Modifications and advancements led to a 10-species subgingival model often combined with human gingival epithelial cells, as an integral part of the oral innate immune system, eliciting various cell responses ranging from cytokine production to apoptosis. In conclusion, biofilm models enable a multitude of questions to be addressed that cannot be studied with planktonic monocultures. The Zurich in vitro biofilm models are reproducible and reliable and may be used for basic studies, but also for application-oriented questions that could not be addressed using culture techniques. Oral biofilm research will certainly lead to a more realistic assessment of the role of microorganisms in the oral cavity in health and disease. In this respect, substantial progress has been made, but there is still more to explore.